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Potempa M, Hart PC, Rajab IM, Potempa LA. Redefining CRP in tissue injury and repair: more than an acute pro-inflammatory mediator. Front Immunol 2025; 16:1564607. [PMID: 40093010 PMCID: PMC11906453 DOI: 10.3389/fimmu.2025.1564607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 02/13/2025] [Indexed: 03/19/2025] Open
Abstract
Most early studies investigating the role of C-reactive protein (CRP) in tissue damage determined it supported pro-hemostatic and pro-inflammatory activities. However, these findings were not universal, as other data suggested CRP inhibited these same processes. A potential explanation for these disparate observations finally emerged with the recognition that CRP undergoes context-dependent conformational changes in vivo, and each of its three isoforms - pentameric CRP (pCRP), modified pentameric CRP (pCRP*), and monomeric CRP (mCRP) - have different effects. In this review, we consider this new paradigm and re-evaluate the role of CRP and its isoforms in the tissue repair process. Indeed, a growing body of evidence points toward the involvement of CRP not just in hemostasis and inflammation, but also in the resolution of inflammation and in tissue regeneration. Additionally, we briefly discuss the shortcomings of the currently available diagnostic tests for CRP and highlight the need for change in how CRP is currently utilized in clinical practice.
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Affiliation(s)
| | - Peter C. Hart
- College of Science, Health, and Pharmacy, Roosevelt University, Schaumburg, IL, United States
| | - Ibraheem M. Rajab
- College of Science, Health, and Pharmacy, Roosevelt University, Schaumburg, IL, United States
| | - Lawrence A. Potempa
- Acphazin Inc., Deerfield, IL, United States
- College of Science, Health, and Pharmacy, Roosevelt University, Schaumburg, IL, United States
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Vennam SS, Talevi V, Venkataraman G, Syed RA, Zhang X, Mass BB, Voruganti VS. A Pilot Study to Evaluate the Role of Obesity and Genetic Variants in Serum C-Reactive Protein Response to an Acute Fructose Load. Lifestyle Genom 2025; 18:64-75. [PMID: 40015263 DOI: 10.1159/000544832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 01/31/2025] [Indexed: 03/01/2025] Open
Abstract
INTRODUCTION Excess fructose intake has been linked to increased risk of dyslipidemia, insulin resistance, hyperuricemia, inflammation, and obesity. In this human study, we investigated if serum C-reactive protein (CRP) concentrations change after fructose consumption, and whether genetic variants and obesity status influence this change. METHODS Blood was drawn before and at four time points after administration of a fructose load (n = 57). Serum concentrations of CRP were measured, and 11 single nucleotides polymorphisms (SNPs) (rs1205, rs1417938, rs1470515, rs3093068, rs6588158, rs16842568, rs2259820, rs157581, rs2794521, rs3093062, rs17700633), previously associated with serum CRP were genotyped and assessed for their association with CRP levels. RESULTS Participants identifying as White (n = 37) had higher mean CRP levels across all time points compared to those identifying as Black (n = 20). Participants with obesity (body mass index ≥30 kg/m2) (n = 25) were younger and had higher mean CRP levels throughout the study period compared to those without (n = 32). All SNPs were in Hardy-Weinberg equilibrium and their effect allele frequencies ranged between 11 and 96%. Baseline CRP was associated with CRP SNPs rs1417938 and rs2794521 (p < 0.005); rs2794521 was also associated with CRP response to fructose challenge (p < 0.005). The variability in response to fructose and genetic associations was mainly observed in individuals without obesity. Obesity status was associated with early changes in CRP (0-30 min and 30-60 min) whereas CRP SNPs were associated with later changes (60-120 min and 120-180 min). CONCLUSION Changes in serum CRP were associated with obesity status or SNPs based on the time elapsed since fructose ingestion. Larger studies are needed to confirm and validate these associations.
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Affiliation(s)
- Sai Sravani Vennam
- Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Valentina Talevi
- Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | | | | | - Xinruo Zhang
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Baba B Mass
- Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Venkata Saroja Voruganti
- Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Vogi V, Haschka D, Forer L, Schwendinger S, Petzer V, Coassin S, Tancevski I, Sonnweber T, Löffler-Ragg J, Puchhammer-Stöckl E, Graninger M, Wolf D, Kronenberg F, Zschocke J, Jukic E, Weiss G. Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations. Sci Rep 2025; 15:4708. [PMID: 39922945 PMCID: PMC11807156 DOI: 10.1038/s41598-025-89306-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/04/2025] [Indexed: 02/10/2025] Open
Abstract
A hyperinflammatory state with highly elevated concentrations of inflammatory biomarkers such as C-reactive protein (CRP) is a characteristic feature of severe coronavirus disease 2019 (COVID-19). To examine a potential role of common genetic factors that may influence COVID-19 outcomes, we investigated whether individuals with a polygenic predisposition for a pro-inflammatory response (in the form of Polygenic Scores) are more likely to develop severe COVID-19. The innovative approach of polygenic scores to investigate genetic factors in COVID-19 severity should provide a comprehensive approach beyond single-gene studies. In our cohort of 156 patients of European ancestry, two overlapping Polygenic Scores (PGS) predicting a genetic predisposition to basal CRP concentrations were significantly different between non-severe and severe COVID-19 cases and were associated with less severe COVID-19 outcomes. Furthermore, specific single nucleotide polymorphisms (SNPs) that contribute to either of the two Polygenic Scores predicting basal CRP levels are associated with different traits that represent risk factors for COVID-19 disease initiation (ACE2 receptor, viral replication) and progression (CRP). We suggest that genetically determined enforced CRP formation may contribute to strengthening of innate immune responses and better initial pathogen control thereby reducing the risk of subsequent hyperinflammation and adverse course of COVID-19.
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Affiliation(s)
- Verena Vogi
- Institute of Human Genetics, Medical University Innsbruck, Innsbruck, 6020, Austria
| | - David Haschka
- Department of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Lukas Forer
- Institute of Genetic Epidemiology, Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Simon Schwendinger
- Institute of Human Genetics, Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Verena Petzer
- Department of Internal Medicine V (Hematology and Internistic Oncology), Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Stefan Coassin
- Institute of Genetic Epidemiology, Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Ivan Tancevski
- Department of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Thomas Sonnweber
- Department of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Judith Löffler-Ragg
- Department of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University Innsbruck, Innsbruck, 6020, Austria
| | | | - Marianne Graninger
- Department of Virology, Medical University Vienna, Vienna, 1090, Austria
| | - Dominik Wolf
- Department of Internal Medicine V (Hematology and Internistic Oncology), Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Florian Kronenberg
- Institute of Genetic Epidemiology, Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Johannes Zschocke
- Institute of Human Genetics, Medical University Innsbruck, Innsbruck, 6020, Austria
| | - Emina Jukic
- Institute of Human Genetics, Medical University Innsbruck, Innsbruck, 6020, Austria.
| | - Günter Weiss
- Department of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University Innsbruck, Innsbruck, 6020, Austria.
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Wang R, Li Y, Jiang Y, Liu X, Feng H, Jiao Z, Li B, Liu C, Shen Y, Chu F, Zhu C, Sun D, Zhang W. Interaction study of the effects of environmental exposure and gene polymorphisms of inflammatory and immune-active factors on chronic obstructive pulmonary disease. Respir Res 2025; 26:5. [PMID: 39780163 PMCID: PMC11707857 DOI: 10.1186/s12931-024-03079-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, influenced by both environmental and genetic factors. Single nucleotide polymorphism (SNP) in the human genome may influence the risk of developing COPD and the response to treatment. We assessed the effects of gene polymorphism of inflammatory and immune-active factors and gene-environment interaction on risk of COPD in middle-aged and older Chinese individuals. METHODS In this community-based case-control study, 471 patients with COPD and 485 controls aged 40-76 years in Heilongjiang Province, China were included. Face-to-face interviews, lung function tests, and multiplex polymerase chain reaction were used to obtain data. Logistic regression model, generalized multifactor dimensionality reduction and crossover analysis were used to analyse the effects of SNPs, gene-gene interactions, and gene-environment interactions on COPD. RESULTS CRP gene[rs1130864-A allele (OR, 1.77; 95% CI 1.11-2.81); G/A + A/A genotype (OR, 1.75; 95% CI 1.07-2.84)], FCAR gene[rs4806606-G (OR, 0.72; 95% CI 0.53-0.98); rs8112766-G (OR, 0.79; 95% CI 0.64-0.98)] and FCGR2A gene[rs4656308-C (OR, 0.74; 95% CI 0.55-1.00); rs4656309-T (OR, 0.81; 95% CI 0.66-0.99)] are independent influential factors for COPD. Rs1205 [RERI: 0.15 (0.07-1.00)] and rs1130864 [RERI: 2.45 (0.73-4.18)] of CRP gene, rs11084376 [OR: 0.54 (0.29-0.97)] of FCAR gene, rs844 of FCGR2B [SI: 0.30 (0.11-0.77); OR: 0.46 (0.24-0.90)] gene, rs4656308-rs4656309-rs2165088 haplotype [SI: 0.48 (0.26-0.89)] of FCGR2A gene and exposure to smoking index > 200, indoor coal/wood/straw use, and outdoor straw burning play synergistic or antagonistic roles in the development of COPD. CONCLUSIONS Alleles and genotypes of the CRP/FCAR/FCGR2A gene can increase the susceptibility to COPD in the northern Chinese population. For the first time, environmental exposure to the CRP/FCAR/FCGR2A/FCGR2B genes has been shown to have synergistic or antagonistic effects on COPD susceptibility on genotypes or haplotypes.
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Affiliation(s)
- Rui Wang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- School of Medical Science and Laboratory Medicine, Jiangsu College of Nursing, Huai'an, 223005, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Yuanyuan Li
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Yuting Jiang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Xiaona Liu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Hongqi Feng
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Zhe Jiao
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Bingyun Li
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Chang Liu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Yuncheng Shen
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Fang Chu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Chenpeng Zhu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Dianjun Sun
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China.
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China.
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China.
- State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin Medical University, Harbin, 150081, People's Republic of China.
| | - Wei Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, 150081, People's Republic of China.
- NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, 150081, People's Republic of China.
- Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin, 150081, People's Republic of China.
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Alberto RPJ, Benjamin GN, Elizabeth RMJ, Alberto CDL, Eliseo PDB. Understanding COVID-19-related Acute Renal Injury in Elderly Individuals: Preexisting Systemic Inflammation before COVID-19 (SIC). Endocr Metab Immune Disord Drug Targets 2025; 25:300-309. [PMID: 38919086 DOI: 10.2174/0118715303312433240611093855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 05/14/2024] [Accepted: 05/20/2024] [Indexed: 06/27/2024]
Abstract
In this study, we examined preexisting systemic inflammation before COVID-19 (SIC), as assessed through C-reactive protein (CRP) levels, to gain insights into the origins of acute kidney injury (AKI) in adults with comorbidities affected by COVID-19. Although aging is not categorized as a disease, it is characterized by chronic inflammation, and older individuals typically exhibit higher circulating levels of inflammatory molecules, particularly CRP, compared to younger individuals. Conversely, elevated CRP concentrations in older adults have been linked with the development of comorbidities. Simultaneously, these comorbidities contribute to the production of inflammatory molecules, including CRP. Consequently, older adults with comorbidities have higher CRP concentrations than their counterparts without comorbidities or those with fewer comorbidities. Given that CRP levels are correlated with the development and severity of AKI in non-COVID-19 patients, we hypothesized that individuals with greater SIC are more likely to develop AKI during SARS-CoV-2 infection than those with less SIC.
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Affiliation(s)
- Ruiz-Pacheco Juan Alberto
- Investigador por México-CONAHCYT, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Jalisco, México
| | - Gomez-Navarro Benjamin
- Servicio de Nefrología y Trasplantes, Hospital Country 2000, Guadalajara, Jalisco, México
| | | | - Castillo-Díaz Luis Alberto
- Departamento de Medicina y Ciencias de la Salud, Facultad Interdiciplinaria de Ciencias Biológicas y de la Salud, Universidad de Sonora, Hermosillo, México
| | - Portilla-de Buen Eliseo
- División de Investigación Quirúrgica, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Jalisco, México
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Lopez-Roblero A, Serrano-Guzmán E, Guerrero-Báez RS, Delgado-Enciso I, Gómez-Manzo S, Aguilar-Fuentes J, Ovando-Garay V, Hernández-Ochoa B, Quezada-Cruz IC, Lopez-Lopez N, Canseco-Ávila LM. Single‑nucleotide polymorphisms in the promoter of the gene encoding for C‑reactive protein associated with acute coronary syndrome. Biomed Rep 2024; 21:150. [PMID: 39247423 PMCID: PMC11375626 DOI: 10.3892/br.2024.1838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 07/26/2024] [Indexed: 09/10/2024] Open
Abstract
Acute coronary syndrome (ACS) is a leading cause of mortality worldwide. Several studies have shown that certain single nucleotide polymorphisms (SNPs) are linked to the development of ACS. In particular, C-reactive protein (CRP) has emerged as an important predictive biomarker for cardiovascular disease. The current study aimed to investigate four polymorphisms of the CRP gene as possible biomarkers for ACS in a sample of 252 individuals (114 patients with ACS and 138 healthy controls) from Southeastern Mexico. Multivariate analysis adjusted for clinical variables showed that the polymorphism 3872CT for the genotype CC/CT [adjusted Odds Ratio (AdOR)=3.78; 95% Confidence Interval (CI): 1.11-12.92; P=0.034] and the genotype GG/GC of the polymorphisms 2667CG (AdOR=4.82; 95% CI: 1.69-13.72; P=0.02) were associated with ACS. However, the polymorphisms 3006AC genotype AA/AC and 5237GA genotype GG/GC were not found to be associated in the multivariate analysis with ACS (P>0.05). These results suggested that 3872CC/CT and 2667CC/CG polymorphism of the CRP gene plays a significant role in the development of ACS.
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Affiliation(s)
- Alexander Lopez-Roblero
- Diagnostic and Molecular Biomedicine Laboratory, Faculty of Chemistry Sciences, Campus IV, Autonomous University of Chiapas, Tapachula, Chiapas 30700, México
| | - Eleazar Serrano-Guzmán
- Diagnostic and Molecular Biomedicine Laboratory, Faculty of Chemistry Sciences, Campus IV, Autonomous University of Chiapas, Tapachula, Chiapas 30700, México
- Regional High Specialty Hospital, Tapachula, Chiapas 30700, México
| | - Rocío Stephania Guerrero-Báez
- Diagnostic and Molecular Biomedicine Laboratory, Faculty of Chemistry Sciences, Campus IV, Autonomous University of Chiapas, Tapachula, Chiapas 30700, México
| | - Iván Delgado-Enciso
- Cancerology State Institute, Colima State Health Services, Colima 28085, México
- School of Medicine, University of Colima, Colima 28040, México
| | - Saúl Gómez-Manzo
- Genetic Biochemistry Laboratory, National Institute of Pediatrics, Ministry of Health, México City 04530, México
| | - Javier Aguilar-Fuentes
- Faculty of Agricultural Sciences, Autonomous University of Chiapas, Huehuetán, Chiapas 30660, México
| | - Vivían Ovando-Garay
- Faculty of Medicine, Campus IV, Autonomous University of Chiapas, Tapachula, Chiapas 30700, México
| | - Beatriz Hernández-Ochoa
- Immunochemistry Laboratory, Children's Hospital of México Federico Gómez, Ministry of Health, México City 06720, México
| | | | - Noe Lopez-Lopez
- Diagnostic and Molecular Biomedicine Laboratory, Faculty of Chemistry Sciences, Campus IV, Autonomous University of Chiapas, Tapachula, Chiapas 30700, México
| | - Luis Miguel Canseco-Ávila
- Diagnostic and Molecular Biomedicine Laboratory, Faculty of Chemistry Sciences, Campus IV, Autonomous University of Chiapas, Tapachula, Chiapas 30700, México
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Winful T, Sorunke M, Benn Torres J. Exploring the Relationship Between Stress, Salivary C-Reactive Protein, and Embodied Physiological Responses in a Nigerian Population. Am J Hum Biol 2024; 36:e24158. [PMID: 39318111 DOI: 10.1002/ajhb.24158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 09/02/2024] [Accepted: 09/07/2024] [Indexed: 09/26/2024] Open
Abstract
OBJECTIVES The impacts of stress on inflammation, although hypothesized, have not been thoroughly examined, especially in relation to social and environmental factors and particularly within Black populations. This study aims to explore the biological mechanisms of embodiment linking stress and health to understand physiological changes in the body's response to psychological stress in a Nigerian population. Through a multidisciplinary approach, this study queries the relationship between stress, cortisol, and salivary C-reactive protein (sCRP), a biomarker of inflammation, while also validating the use of sCRP as a potential and accurate stress indicator in the field. METHODS In this cross-sectional study, 138 passive drool saliva samples (n female = 89 n male = 49) were collected and assessed for sCRP and cortisol levels in adults. Participants also completed a short demographic survey and, to measure psychological stress, the General Health Questionnaire 12 (GHQ-12). Relationships between sCRP and stress-related variables (i.e., cortisol, GHQ-12, and demographic data) were assessed using Spearman's correlations, simple regression, multivariable linear regression, and exploratory factor analysis. RESULTS sCRP levels ranged from 20.57 to 6879.41 pg/mL across all samples, with significant differences between female and male participants. The GHQ-12 was not a significant predictor of sCRP variability. However, socio-demographic factors such as body mass index (BMI), age, self-reported sex, ethnic identity, and cortisol were significant predictors, collectively explaining 24%-27% of the variation in sCRP. CONCLUSION Socio-demographic predictors like BMI, age, sex, and particularly ethnic group experience in Nigeria encapsulate aspects of embodied stress, that significantly affect sCRP variability.
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Affiliation(s)
- Taiye Winful
- Department of Anthropology, Genetic Anthropology and Biocultural Studies Laboratory, Vanderbilt University, Nashville, Tennessee, USA
- Department of Anthropology, University of Illinois Urbana Champaign, Champaign, Illinois, USA
| | - Modupe Sorunke
- Department of Preventive Dentistry, Lagos State University College of Medicine (LASUCOM), Ikeja-Lagos, Nigeria
| | - Jada Benn Torres
- Department of Anthropology, Genetic Anthropology and Biocultural Studies Laboratory, Vanderbilt University, Nashville, Tennessee, USA
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Turczynowicz A, Jakubów P, Niedźwiecka K, Kondracka J, Pużyńska W, Tałałaj M, Guszczyn T, Grabala P, Kowalczuk O, Kocańda S. Mu-Opioid Receptor 1 and C-Reactive Protein Single Nucleotide Polymorphisms as Biomarkers of Pain Intensity and Opioid Consumption. Brain Sci 2023; 13:1629. [PMID: 38137077 PMCID: PMC10741726 DOI: 10.3390/brainsci13121629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 11/13/2023] [Accepted: 11/20/2023] [Indexed: 12/24/2023] Open
Abstract
Children constitute a special group in pain therapy. Single nucleotide polymorphisms that are associated with differences in postoperative, inflammatory pain perception and opioid requirement are the A118G SNP in the mu-opioid receptor 1 (OPRM1) gene and the rs1205 CRP. This study aimed to determine connection between OPRM1 and rs1205 CRP SNPs in pediatric patients postoperatively and pain intensity, the opioid dose needed to control pain after scoliosis correction, and other clinical aspects. Genotypes of rs1205 CRP and OPRM1 polymorphisms in a sample of 31 patients were specified, and statistical analysis was performed in terms of age, genotype frequency, pain assessment, sufentanil flow, post-anesthesia care unit stay, and the use of coanalgesics. The frequency of A/A and A/G genotypes in the OPRM1 gene was in line with 1000Genomes data for the European population. Patients from the AG group of OPRM1 SNP more frequently required coanalgesics for adequate pain control; however, it was of weak statistical significance. Other parameters measured in the study were not statistically significant in relation to OPRM1 and CRP polymorphisms. The effect of SNPs on postoperative pain management and opioid therapy in children was not confirmed by this study. An expansion of the study sample and other opioid-related SNPs is required.
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Affiliation(s)
- Aleksander Turczynowicz
- Department of Anesthesiology and Intensive Care for Children and Adolescents with Postoperative and Pain Treatment Unit, Medical University of Bialystok, 15-274 Bialystok, Poland; (P.J.); (J.K.); (M.T.)
| | - Piotr Jakubów
- Department of Anesthesiology and Intensive Care for Children and Adolescents with Postoperative and Pain Treatment Unit, Medical University of Bialystok, 15-274 Bialystok, Poland; (P.J.); (J.K.); (M.T.)
| | - Karolina Niedźwiecka
- Department of Cardiosurgery, Medical University of Bialystok, 15-276 Bialystok, Poland; (K.N.)
| | - Julia Kondracka
- Department of Anesthesiology and Intensive Care for Children and Adolescents with Postoperative and Pain Treatment Unit, Medical University of Bialystok, 15-274 Bialystok, Poland; (P.J.); (J.K.); (M.T.)
| | - Weronika Pużyńska
- Department of Palliative Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland;
| | - Mariola Tałałaj
- Department of Anesthesiology and Intensive Care for Children and Adolescents with Postoperative and Pain Treatment Unit, Medical University of Bialystok, 15-274 Bialystok, Poland; (P.J.); (J.K.); (M.T.)
| | - Tomasz Guszczyn
- Department of Pediatric Orthopedics and Traumatology, Medical University of Bialystok, 15-274 Bialystok, Poland; (T.G.); (P.G.)
| | - Paweł Grabala
- Department of Pediatric Orthopedics and Traumatology, Medical University of Bialystok, 15-274 Bialystok, Poland; (T.G.); (P.G.)
| | - Oksana Kowalczuk
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland
| | - Szymon Kocańda
- Department of Cardiosurgery, Medical University of Bialystok, 15-276 Bialystok, Poland; (K.N.)
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9
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Mouliou DS. C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians. Diseases 2023; 11:132. [PMID: 37873776 PMCID: PMC10594506 DOI: 10.3390/diseases11040132] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/25/2023] Open
Abstract
The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.
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10
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D’Incà R, Sturniolo G. Biomarkers in IBD: What to Utilize for the Diagnosis? Diagnostics (Basel) 2023; 13:2931. [PMID: 37761298 PMCID: PMC10527829 DOI: 10.3390/diagnostics13182931] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/05/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process; the performance is better in Crohn's disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap, but the long half-life, the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.
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Affiliation(s)
- Renata D’Incà
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35124 Padua, Italy
| | - Giulia Sturniolo
- Department of Women’s and Children’s Health, University of Padua, 35128 Padova, Italy
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11
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Schulz S, Rehm S, Schlitt A, Lierath M, Lüdike H, Hofmann B, Bitter K, Reichert S. C-Reactive Protein Level and the Genetic Variant rs1130864 in the CRP Gene as Prognostic Factors for 10-Year Cardiovascular Outcome. Cells 2023; 12:1775. [PMID: 37443809 PMCID: PMC10341152 DOI: 10.3390/cells12131775] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 06/29/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) is the primary cause of premature death and disability worldwide. There is extensive evidence that inflammation represents an important pathogenetic mechanism in the development and prognosis of CVD. C-reactive protein (CRP) is a potential marker of vascular inflammation and plays a direct role in CVD by promoting vascular inflammation. The objective of this study (ClinTrials.gov identifier: NCT01045070) was to assess the prognostic impact of CRP protein levels and genetic variants of CRP gene events on cardiovascular (CV) outcome (10-year follow-up) in patients suffering from CVD. METHODS CVD patients were prospectively included in this study (n = 1002) and followed up (10 years) regarding combined CV endpoint (CV death, death from stroke, myocardial infarction (MI), and stroke/transient ischemic attack (TIA)). CRP protein level (particle-enhanced immunological turbidity test) and genetic variants (rs1130864, rs1417938, rs1800947, rs3093077; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) after DNA extraction from EDTA-blood) were evaluated. RESULTS In survival analyses, increased CRP protein levels of ≥5 mg/L (log-rank test: p < 0.001, Cox regression: p = 0.002, hazard ratio = 1.49) and CT + TT genotype of rs1130864 (log-rank test: p = 0.041; Cox regression: p = 0.103, hazard ratio = 1.21) were associated with a weaker CV prognosis considering combined CV endpoint. CONCLUSIONS Elevated CRP level and genetic variant (rs1130864) were proven to provide prognostic value for adverse outcome in CVD patients within the 10-year follow-up period.
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Affiliation(s)
- Susanne Schulz
- Department of Operative Dentistry and Periodontology, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany; (S.R.); (M.L.); (H.L.); (K.B.); (S.R.)
| | - Selina Rehm
- Department of Operative Dentistry and Periodontology, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany; (S.R.); (M.L.); (H.L.); (K.B.); (S.R.)
| | - Axel Schlitt
- Department of Cardiology, Paracelsus-Harz-Clinic Bad Suderode, 06485 Quedlinburg, Germany;
- Department of Medicine III, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany
| | - Madlen Lierath
- Department of Operative Dentistry and Periodontology, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany; (S.R.); (M.L.); (H.L.); (K.B.); (S.R.)
| | - Henriette Lüdike
- Department of Operative Dentistry and Periodontology, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany; (S.R.); (M.L.); (H.L.); (K.B.); (S.R.)
| | - Britt Hofmann
- Department of Cardiothoracic Surgery, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany;
| | - Kerstin Bitter
- Department of Operative Dentistry and Periodontology, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany; (S.R.); (M.L.); (H.L.); (K.B.); (S.R.)
| | - Stefan Reichert
- Department of Operative Dentistry and Periodontology, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany; (S.R.); (M.L.); (H.L.); (K.B.); (S.R.)
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12
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Lin CC, Li CI, Liu CS, Liao LN, Yang CW, Lin CH, Yang SY, Li TC. Association of high-sensitivity C-reactive protein and diabetic nephropathy in patients with type 2 diabetes: a Mendelian randomization study. BMJ Open Diabetes Res Care 2023; 11:e003197. [PMID: 36828641 PMCID: PMC9971832 DOI: 10.1136/bmjdrc-2022-003197] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 02/09/2023] [Indexed: 02/26/2023] Open
Abstract
INTRODUCTION Observational studies support the relationship between C-reactive protein (CRP) level and diabetic nephropathy (DN) in patients with diabetes. The research question regarding whether the relationship between serum high-sensitivity C-reactive protein (hsCRP) level and DN is causal lacks experimental evidence. Therefore, this study aimed to evaluate the causality between hsCRP and DN based on Mendelian randomization (MR) analysis. RESEARCH DESIGN AND METHODS A total of 2332 participants with type 2 diabetes from the Taiwan Biobank database was analyzed. Genetic risk scores (GRSs), which comprise four validated CRP loci as two instrumental variables, were calculated as unweighted and weighted scores to evaluate the causal relationship of hsCRP with DN risk. The two-stage regression model was used to estimate OR and 95% CI. RESULTS The analyses of the observational study showed that the hsCRP level was significantly associated with DN after multivariate adjustment (adjusted OR 1.15; 95% CI 1.01 to 1.32). Unweighted/weighted GRSs for log-transformed hsCRP satisfied MR assumptions 1 and 3, respectively; that is, a significant association with hsCRP was observed but that with DN was absent (adjusted OR 1.00, 95% CI 0.92 to 1.09; 1.00, 0.72 to 1.39, respectively). The MR analyses demonstrated that a 1-unit increase in the log-transformed genetically predicted hsCRP by unweighted and weighted GRSs was associated with DN, demonstrating ORs of 1.80 (95% CI 1.51 to 2.14) and 1.67 (95% CI 1.40 to 1.98), respectively. CONCLUSIONS The current study provided experimental evidence that hsCRP level was causally related to DN. These findings suggest that the elevated hsCRP may be a causal risk factor for DN in patients with type 2 diabetes.
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Affiliation(s)
- Cheng-Chieh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Ing Li
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Chiu-Shong Liu
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Li-Na Liao
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Chuan-Wei Yang
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsueh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Shing-Yu Yang
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
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13
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Chen Z, Jiang F, Yang M, Yang J. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis. Open Life Sci 2022; 17:1519-1530. [DOI: 10.1515/biol-2022-0505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 08/28/2022] [Accepted: 09/04/2022] [Indexed: 11/17/2022] Open
Abstract
Abstract
Ischemic stroke (IS), usually caused due to an abrupt blockage of an artery, is the leading cause of disability and the second leading cause of death worldwide. The association of the C-reactive protein (CRP) gene (s3093059 T/C and rs1205 C/T) polymorphisms and IS susceptibility has been widely studied, but the results remain inconsistent. Our study aimed to assess the association between CRP gene (s3093059 T/C and rs1205 C/T) polymorphisms and IS risk. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang databases were searched up to April 2022 to identify eligible studies. The Newcastle-Ottawa scale (NOS) score was calculated to assess study quality. The odd ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between CRP gene (rs3093059 T/C and rs1205 C/T) polymorphisms and IS risk. Eighteen case–control studies with 6339 cases and 29580 controls were identified. We found that CRP (s3093059 T/C and rs1205 C/T) polymorphism was not significantly associated with the risk of IS in any genetic model (recessive model: OR 1.00, 95% CI 0.79–1.26; OR 1.06, 95% CI 0.90–1.25). When stratified analysis by country, genotype method, source of controls, and NOS score, still no statistically significant association was found. Our study indicated that the CRP (rs3093059 T/C and rs1205 C/T) polymorphisms were not associated with the susceptibility to IS.
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Affiliation(s)
- Zhizhi Chen
- Department of Neurology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital , Quzhou 324000 , Zhejiang , China
| | - Feifei Jiang
- Department of Neurology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital , Quzhou 324000 , Zhejiang , China
| | - Ming Yang
- Department of Neurology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital , Quzhou 324000 , Zhejiang , China
| | - Jie Yang
- Department of Rehabilitation Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital , 100 Minjiang Road , Quzhou 324000 , Zhejiang , China
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Balzanelli MG, Distratis P, Lazzaro R, Pham VH, Tran TC, Dipalma G, Bianco A, Serlenga EM, Aityan SK, Pierangeli V, Nguyen KCD, Inchingolo F, Tomassone D, Isacco CG. Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection. Diagnostics (Basel) 2022; 12:diagnostics12112824. [PMID: 36428884 PMCID: PMC9689844 DOI: 10.3390/diagnostics12112824] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/07/2022] [Accepted: 11/10/2022] [Indexed: 11/18/2022] Open
Abstract
Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual's responses to the virus and the high differences of effect that the virus may cause to some. While a person's preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts' genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO2 and carbon dioxide-SpCO2) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1β, IL1RN (IL-1 β and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.
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Affiliation(s)
- Mario Giosuè Balzanelli
- SET-118, Department of Pre-Hospital and Emergency-San Giuseppe Moscati Hospital, 74100 Taranto, Italy
| | - Pietro Distratis
- SET-118, Department of Pre-Hospital and Emergency-San Giuseppe Moscati Hospital, 74100 Taranto, Italy
| | - Rita Lazzaro
- SET-118, Department of Pre-Hospital and Emergency-San Giuseppe Moscati Hospital, 74100 Taranto, Italy
| | - Van Hung Pham
- Department of Microbiology and Virology, Phan Chau Trinh University of Medicine, Danang City 50000, Vietnam
| | - Toai Cong Tran
- Department of Histology, Embryology and Genetics, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 70000, Vietnam
| | - Gianna Dipalma
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
| | - Angelica Bianco
- Experimental Zooprophylactic Institute of Puglia and Basilicata, 71121 Foggia, Italy
| | - Emilio Maria Serlenga
- Hematology Department, Blood Transfusion Unit, SS Annunnziata Hospital, 74100 Taranto, Italy
| | | | | | - Kieu Cao Diem Nguyen
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
| | - Diego Tomassone
- Foundation of Physics Research Center, 87053 Celico, Italy
- Correspondence:
| | - Ciro Gargiulo Isacco
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70126 Bari, Italy
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Scholl JL, King ZR, Pearson K, Kallsen NA, Ehli EA, Fercho KA, Brown-Rice KA, Forster GL, Baugh LA. Methylation of genes and regulation of inflammatory processes on emotional response in young adults with alcoholic parents. Brain Behav Immun Health 2022; 25:100505. [PMID: 36110145 PMCID: PMC9468507 DOI: 10.1016/j.bbih.2022.100505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 10/31/2022] Open
Abstract
Many Americans are adult children of an alcoholic parent (ACoA), which can confer an increased risk of trauma and hazardous alcohol use, as well as heritable and environmental genetic influence. Psychological health and related neural activity can be influenced by inflammation responses, but it is not clear how these factors interact regarding risk or resilience to hazardous alcohol use. The goals of this study were to better understand the relationships between current alcohol use and inflammation, how these are modified by single nucleotide polymorphisms (SNPs) and/or epigenetic modifications of inflammation-associated genes; and how these alter neural reactivity to emotionally-salient stimuli. To do so, ACoA participants were dichotomized as resilient (not engaged in hazardous alcohol use) or vulnerable (currently engaged in hazardous alcohol use). Measures of blood-oxygen-level-dependent (BOLD) activity within regions of interest (ROIs), SNPs and DNA methylation of specific inflammation regulatory genes, and biological markers of inflammation were compared between these groups. Vulnerable ACoAs exhibited higher plasma C-reactive protein (CRP) and greater BOLD activity in the right hippocampus and ventral anterior cingulate cortex in response to emotional cues as well as reduced methylation of CRP and glucocorticoid-related genes. Path analysis revealed significant relationships between alcohol use, SNPs, DNA methylation of inflammatory-related genes, CRP levels, and BOLD activity to emotional stimuli. Taken together, these findings suggest a complex association related to hazardous alcohol use in ACoAs that may predict current inflammation and neural reactivity to emotional stimuli. A better understanding of these associations could direct the future of individual treatment options.
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Affiliation(s)
- Jamie L. Scholl
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
| | - Zach R. King
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
| | - Kami Pearson
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
| | | | - Erik A. Ehli
- Avera Institute for Human Genetics, Sioux Falls, SD, USA
| | | | - Kathleen A. Brown-Rice
- Department of Counselor Education, College of Education, Sam Houston State University, Huntsville, TX, USA
| | - Gina L. Forster
- Department of Anatomy, University of Otago, Dunedin, New Zealand
| | - Lee A. Baugh
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
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16
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Misra DP, Jain N, Ora M, Singh K, Agarwal V, Sharma A. Outcome Measures and Biomarkers for Disease Assessment in Takayasu Arteritis. Diagnostics (Basel) 2022; 12:diagnostics12102565. [PMID: 36292253 PMCID: PMC9601573 DOI: 10.3390/diagnostics12102565] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 12/05/2022] Open
Abstract
Takayasu arteritis (TAK) is a less common large vessel vasculitis where histopathology of involved arteries is difficult to access except during open surgical procedures. Assessment of disease activity in TAK, therefore, relies on surrogate measures. Clinical disease activity measures such as the National Institutes of Health (NIH) score, the Disease Extent Index in TAK (DEI.TAK) and the Indian TAK Clinical Activity Score (ITAS2010) inconsistently associate with acute phase reactants (APRs). Computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), or color Doppler Ultrasound (CDUS) enables anatomical characterization of stenosis, dilatation, and vessel wall characteristics. Vascular wall uptake of 18-fluorodeoxyglucose or other ligands using positron emission tomography computerized tomography (PET-CT) helps assess metabolic activity, which reflects disease activity well in a subset of TAK with normal APRs. Angiographic scoring systems to quantitate the extent of vascular involvement in TAK have been developed recently. Erythrocyte sedimentation rate and C-reactive protein have a moderate performance in distinguishing active TAK. Numerous novel biomarkers are under evaluation in TAK. Limited literature suggests a better assessment of active disease by combining APRs, PET-CT, and circulating biomarkers. Validated damage indices and patient-reported outcome measures specific to TAK are lacking. Few biomarkers have been evaluated to reflect vascular damage in TAK and constitute important research agenda.
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Affiliation(s)
- Durga Prasanna Misra
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India
- Correspondence: (D.P.M.); (A.S.)
| | - Neeraj Jain
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India
| | - Manish Ora
- Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India
| | - Kritika Singh
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India
| | - Vikas Agarwal
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India
| | - Aman Sharma
- Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
- Correspondence: (D.P.M.); (A.S.)
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17
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Genetic variation in C-reactive protein (CRP) gene is associated with retinopathy and hypertension in adolescents with type 1 diabetes. Cytokine 2022; 160:156025. [PMID: 36122502 DOI: 10.1016/j.cyto.2022.156025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 02/10/2022] [Accepted: 08/26/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Elevated concentration of CRP has been associated with the risk of diabetes as well as cardiovascular events and microvascular complications in T1D patients. We hypothesize that the +1846 C > T CRP gene polymorphism may have impact on the risk of T1D and/or its complications. METHODS We have examined 400 young patients with T1D and 250 healthy age-matched controls. The +1846 C > T CRP gene polymorphism was genotyped by ARMS-PCR method. The analysis covers microvascular complications, concentrations of serum pro- and anti-inflammatory markers, adhesion molecules, proangiogenic factor as well as blood pressure. RESULTS CT genotype (OR = 1.799) and T allele (OR = 1.733) are associated with increased risk of T1D, while CC genotype decreases the risk of this condition (OR = 0.458). Moreover, increased risk of hypertension corresponds with TT and T variant (OR = 3.116 and OR = 1.830, resp.) while CC genotype is decreasing the risk (OR = 0.547). Furthermore, CT variant is connected with lower risk of retinopathy (OR = 0.512) whereas TT variant decreases the risk of this complication (OR = 2.228). Our data also implies various effects of CRP +1846 C > T polymorphism on the inflammatory status of T1D patients. CONCLUSIONS Although further studies are required, the +1846 C > T CRP gene polymorphism could be considered a genetic marker to predict susceptibility to retinopathy and hypertension in T1D adolescents.
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18
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Picod A, Morisson L, de Roquetaillade C, Sadoune M, Mebazaa A, Gayat E, Davison BA, Cotter G, Chousterman BG. Systemic Inflammation Evaluated by Interleukin-6 or C-Reactive Protein in Critically Ill Patients: Results From the FROG-ICU Study. Front Immunol 2022; 13:868348. [PMID: 35634339 PMCID: PMC9134087 DOI: 10.3389/fimmu.2022.868348] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/28/2022] [Indexed: 01/08/2023] Open
Abstract
BackgroundThe prognostic impact of high concentration of interleukin-6 (IL-6) or C-reactive protein (CRP), two routinely available markers of systemic inflammation in the general population of critically ill patients, remains unclear. In a large cohort of critically ill patients including septic and non-septic patients, we assessed the relationship between baseline IL-6 or CRP and mortality, organ dysfunction, and the need for organ support.MethodsThis was an ancillary analysis of the prospective French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study including patients with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following intensive care unit (ICU) admission. The primary objective was to determine the association between baseline IL-6 or CRP concentration and survival until day 90. Secondary outcomes included organ dysfunction as evaluated by the Sequential Organ Failure Assessment (SOFA) score, and the need for organ support, including vasopressors/inotropes and/or renal replacement therapy (RRT).ResultsMedian IL-6 and CRP concentrations (n = 2,076) at baseline were 100.9 pg/ml (IQR 43.5–261.7) and 143.7 mg/L (IQR 78.6–219.8), respectively. Day-90 mortality was 30%. High IL-6 or CRP was associated with worse 90-day survival (hazard ratios 1.92 [1.63–2.26] and 1.21 [1.03–1.41], respectively), after adjustment on the Simplified Acute Physiology Score II (SAPS-II). High IL-6 was also associated with the need for organ-support therapies, such as vasopressors/inotropes (OR 2.67 [2.15–3.31]) and RRT (OR 1.55 [1.26–1.91]), including when considering only patients independent from those supports at the time of IL-6 measurement. Associations between high CRP and organ support were inconsistent.ConclusionIL-6 appears to be preferred over CRP to evaluate critically ill patients’ prognoses.
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Affiliation(s)
- Adrien Picod
- Department of Anesthesiology, Burn and Critical Care, University Hospitals Saint-Louis—Lariboisière, AP-HP, Paris, France
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
- Sorbonne University, Paris, France
- *Correspondence: Adrien Picod,
| | - Louis Morisson
- Department of Anesthesiology and Pain Medicine, Hôpital Maisonneuve-Rosemont, CIUSSS de l’Est de l’Ile de Montréal, Montréal, QC, Canada
| | - Charles de Roquetaillade
- Department of Anesthesiology, Burn and Critical Care, University Hospitals Saint-Louis—Lariboisière, AP-HP, Paris, France
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
| | - Malha Sadoune
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
| | - Alexandre Mebazaa
- Department of Anesthesiology, Burn and Critical Care, University Hospitals Saint-Louis—Lariboisière, AP-HP, Paris, France
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
| | - Etienne Gayat
- Department of Anesthesiology, Burn and Critical Care, University Hospitals Saint-Louis—Lariboisière, AP-HP, Paris, France
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
| | - Beth A. Davison
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
- Momentum Research Inc., Durham, NC, United States
| | - Gad Cotter
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
- Momentum Research Inc., Durham, NC, United States
| | - Benjamin Glenn Chousterman
- Department of Anesthesiology, Burn and Critical Care, University Hospitals Saint-Louis—Lariboisière, AP-HP, Paris, France
- UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Markers in Stressed Conditions (MASCOT), Paris University, Paris, France
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Fransén K, Pettersson C, Hurtig-Wennlöf A. CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study. BMC Cardiovasc Disord 2022; 22:170. [PMID: 35428187 PMCID: PMC9013148 DOI: 10.1186/s12872-022-02610-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 04/01/2022] [Indexed: 11/12/2022] Open
Abstract
Background The C-reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide polymorphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardiovascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels or early signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influence of five genetic variants on both plasma CRP levels and carotid intima-media thickness (cIMT) values, including aspects on estrogen containing contraceptive use in females. Methods Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serum levels in 780 Swedish young, self-reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASE v 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self-reported. Results Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, and rs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effect of genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non-carriers. This was specifically pronounced in the estrogen-using group (p < 0.001), and they had also higher cIMT (p = 0.002) than non-carriers but with a small cIMT difference between the haplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using group was observed (r = 0.194; p = 0.026). Conclusions Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels. Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and a marginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage could be involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and the observed difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies may shed further light on the role of more long-term estrogen use and early atherosclerosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-022-02610-z.
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Sanderson E, Glymour MM, Holmes MV, Kang H, Morrison J, Munafò MR, Palmer T, Schooling CM, Wallace C, Zhao Q, Smith GD. Mendelian randomization. NATURE REVIEWS. METHODS PRIMERS 2022; 2:6. [PMID: 37325194 PMCID: PMC7614635 DOI: 10.1038/s43586-021-00092-5] [Citation(s) in RCA: 770] [Impact Index Per Article: 256.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/21/2021] [Indexed: 06/17/2023]
Abstract
Mendelian randomization (MR) is a term that applies to the use of genetic variation to address causal questions about how modifiable exposures influence different outcomes. The principles of MR are based on Mendel's laws of inheritance and instrumental variable estimation methods, which enable the inference of causal effects in the presence of unobserved confounding. In this Primer, we outline the principles of MR, the instrumental variable conditions underlying MR estimation and some of the methods used for estimation. We go on to discuss how the assumptions underlying an MR study can be assessed and give methods of estimation that are robust to certain violations of these assumptions. We give examples of a range of studies in which MR has been applied, the limitations of current methods of analysis and the outlook for MR in the future. The difference between the assumptions required for MR analysis and other forms of non-interventional epidemiological studies means that MR can be used as part of a triangulation across multiple sources of evidence for causal inference.
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Affiliation(s)
- Eleanor Sanderson
- Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - M. Maria Glymour
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Michael V. Holmes
- Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- MRC Population Health Research Unit, University of Oxford, Oxford, UK
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Hyunseung Kang
- Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA
| | - Jean Morrison
- Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
| | - Marcus R. Munafò
- Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- School of Psychological Science, University of Bristol, Bristol, UK
- National Institute for Health Research (NIHR), Biomedical Research Centre, University of Bristol, Bristol, UK
| | - Tom Palmer
- Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - C. Mary Schooling
- School of Public Health, Li Ka Shing, Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- School of Public Health, City University of New York, New York, USA
| | - Chris Wallace
- MRC Biostatistics Unit, University of Cambridge, Cambridge, UK
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge, Cambridge, UK
| | - Qingyuan Zhao
- Statistical Laboratory, University of Cambridge, Cambridge, UK
| | - George Davey Smith
- Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- National Institute for Health Research (NIHR), Biomedical Research Centre, University of Bristol, Bristol, UK
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21
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Bakkaloglu OK, Eskazan T, Celik S, Kurt EA, Hatemi I, Erzin Y, Celik AF. Can we predict mucosal remission in ulcerative colitis more precisely with a redefined cutoff level of C-reactive protein? Colorectal Dis 2022; 24:77-84. [PMID: 34610199 DOI: 10.1111/codi.15940] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 02/08/2023]
Abstract
AIM Most patients with ulcerative colitis (UC) with active mucosal disease have a lower C-reactive protein (CRP) level than the classic accepted cutoff level (≤5 mg/l). We aimed to predict the mucosal remission in UC with an optimal cutoff level of CRP when mucosal activity and extensiveness of UC were both considered. METHOD In this retrospective study, we evaluated CRP values and their relation to mucosal extension and UC activity in 331 colonoscopic examinations performed between December 2016 and March 2019. Endoscopic activity and disease extension were assessed using Mayo scores and the Montreal classification. RESULTS The Mayo 2 and 3 groups' CRP values were significantly higher when compared with Mayo 0-1 between values of E1 and both E2 and E3 with an increasing trend. The standard CRP cutoff level ≤5 mg/l only yielded 55% specificity in predicting mucosal remission. In the ROC analysis, a CRP cutoff level ≤2.9 mg/l predicted an overall mucosal remission (Mayo 0-1) with 77% sensitivity and 80% specificity, and ≤1.9 mg/l predicted Mayo-0 with 70% sensitivity and specificity. In the clinical remission subgroup, the overall CRP cutoff level was even lower, at ≤1.58 mg/l. CONCLUSION An overall CRP cutoff level ≤2.9 mg/l predicts mucosal remission in UC better than the standard cutoff ≤5 mg/l. Mucosal remission in stable clinical remission may present with an even lower CRP level. An increasing trend in the CRP level from E1 through E3 even in mucosal remission suggests that both histological inflammation and extensiveness may have some influence on a CRP-based prediction of endoscopic remission.
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Affiliation(s)
- Oguz Kagan Bakkaloglu
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Tugce Eskazan
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Sinem Celik
- Atasehir Acibadem Hospital, Acibadem University, Istanbul, Turkey
| | - Enes Ali Kurt
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Ibrahim Hatemi
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Yusuf Erzin
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Aykut Ferhat Celik
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
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22
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Chen R, Li L, Li C, Su Y, Zhang Y, Pang X, Zheng J, Zeng Z, Chen MH, Zhang S. Prealbumin and Retinol-Binding Protein 4: The Promising Inflammatory Biomarkers for Identifying Endoscopic Remission in Crohn's Disease. J Inflamm Res 2021; 14:7371-7379. [PMID: 34992423 PMCID: PMC8715867 DOI: 10.2147/jir.s343125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 12/09/2021] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE Endoscopic remission is the primary therapeutic target and associated with clinical outcome in Crohn's disease (CD). Non-invasive and accurate biomarkers are important in monitoring endoscopic remission frequently. Our study aimed at investigating the predictive capacity of prealbumin and retinol-binding protein 4 (RBP4) for identifying endoscopic remission. METHODS From June 2018 to December 2020, 515 endoscopy procedures (332 in the training cohort and 183 in the validation cohort) were enrolled in this multicentre retrospective cohort study. Blood samples were collected for prealbumin or RBP4 testing with 7 days before the endoscopy. A simple Endoscopic Score for CD (SES-CD) was performed to evaluate endoscopic activity and defined endoscopic remission. The area under receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value and negative predictive value were performed to assess the predictive capacity of the biomarkers. RESULTS Serum concentration of prealbumin and RBP4 was demonstrated to be higher in patients with endoscopic remission and significantly negatively correlated with SES-CD in the training cohort. The AUROC of prealbumin and specificity of prealbumin and RBP4 were larger than that of C-reactive protein in the training cohort and the validation cohort. The model combining prealbumin and faecal calprotectin had the largest AUROC (0.842 [95% CI: 0.775-0.908]). Furthermore, in both cohorts, prealbumin had a larger AUROC than C-reactive protein for identifying endoscopic remission in patients with anti-tumour necrosis factor therapy. CONCLUSION Prealbumin and RBP4 were promising biomarkers for identifying endoscopic remission, especially in patients with anti-tumour necrosis factor therapy.
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Affiliation(s)
- Rirong Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Li Li
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Chao Li
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Yuhan Su
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Yingfan Zhang
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Xiaobai Pang
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Jieqi Zheng
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Zhirong Zeng
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Min-Hu Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Shenghong Zhang
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
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C-Reactive Protein +1444C/T Polymorphism Is Associated with the Susceptibility to Pulmonary Tuberculosis. BIOMED RESEARCH INTERNATIONAL 2021; 2020:6634879. [PMID: 33415152 PMCID: PMC7769630 DOI: 10.1155/2020/6634879] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 11/22/2020] [Accepted: 12/14/2020] [Indexed: 12/30/2022]
Abstract
Objective The T allele of C-reactive protein (CRP) +1444C/T (rs1130864) polymorphism was associated with increased risk for some inflammatory conditions. The objective of the study was to explore the association between the CRP +1444C/T polymorphism with the susceptibility to pulmonary tuberculosis (PTB) in a Chinese population. Methods This case-control study enrolled 480 PTB patients and 480 healthy controls. The CRP +1444C/T polymorphism was determined using Sanger sequencing. The odds ratio (OR) and 95% confidence interval (CI) were assessed to examine the strength of genetic correlation. Results The genotype and allele frequencies of PTB patients differed from controls (CT vs. CC, OR = 1.924, 95% CI: 1.099-3.371, adjusted P value = 0.022; T vs. C, OR = 1.884, 95% CI: 1.085-3.273, adjusted P value = 0.024). Stratified analysis by sex found that PTB patients' genotype and allele frequencies differed from controls in the male subgroup but not the female subgroup. Conclusion In conclusion, the minor T allele of CRP +1444C/T polymorphism was associated with increased PTB risk.
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24
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Yang X, Zhang D, Zhao Y, Liu D, Li Q, Guo C, Tian G, Han M, Qie R, Huang S, Zhou Q, Zhao Y, Feng Y, Wu X, Zhang Y, Li Y, Wu Y, Cheng C, Hu D, Sun L. Association between serum level of C-reactive protein and risk of cardiovascular events based on cohort studies. J Hum Hypertens 2021; 35:1149-1158. [PMID: 33980977 DOI: 10.1038/s41371-021-00546-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 04/06/2021] [Accepted: 04/23/2021] [Indexed: 11/09/2022]
Abstract
Although the association between serum level of C-reactive protein (CRP) and risk of cardiovascular events (CVEs) has been reported, the comprehensive assessment of the quantitative association of CRP level with risk of CVEs has not been reported. Our meta-analysis aims to quantitatively evaluate the association of CRP level and risk of CVEs. We searched PubMed and Embase databases for articles published up to December 6, 2019. Studies with data on men and women, different types of CVEs and multiple cohorts within a study were treated as independent studies. Generalized least-squares regression models were used to assess the quantitative association between CRP level and risk of CVEs. Restricted cubic splines were used to model the possible linear association between CRP and CVEs. We included 36 articles (60 studies; 227,715 participants) in the analysis. The pooled relative risks (RRs) of high versus low CRP level for cardiovascular disease (CVD), stroke and coronary heart disease (CHD) were 1.64 (95% confidence interval [CI], 1.49-1.82), 1.46 (95% CI, 1.35-1.58), and 1.55 (95% CI, 1.47-1.63), respectively. A linear association was found between CRP level and CVD (P = 0.429), stroke (P = 0.940), and CHD (P = 0.931); with each 1-mg/L increase in CRP level, the pooled RRs for CVD, stroke, and CHD were 1.18 (95% CI, 1.12-1.24), 1.07 (95% CI, 1.04-1.09), and 1.12 (95% CI, 1.08-1.16), respectively. This meta-analysis suggests that risk of CVEs increases with increasing serum CRP level.
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Affiliation(s)
- Xingjin Yang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Dongdong Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yang Zhao
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Dechen Liu
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.,Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Quanman Li
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Chunmei Guo
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Gang Tian
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Minghui Han
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Ranran Qie
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Shengbing Huang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Qionggui Zhou
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yang Zhao
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yifei Feng
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Xiaoyan Wu
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yanyan Zhang
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yang Li
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yuying Wu
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Cheng Cheng
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Dongsheng Hu
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
| | - Liang Sun
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
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Chen S, Wu Y, Qi H, Shen L, Ma W, Cao F, Diao Y, Wang T, Ou S, Fan W. Single-nodule hepatitis B virus-associated hepatocellular carcinoma smaller than 3 cm: two phenotypes defined by cluster analysis and their association with the outcome of ablation as the first-line therapy. Int J Hyperthermia 2021; 38:120-129. [PMID: 33541160 DOI: 10.1080/02656736.2021.1876930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
OBJECTIVES Hepatocellular carcinoma (HCC) is a heterogeneous disease. This study aimed to identify the heterogeneity related to the prognosis of ablation in patients with single-nodule hepatitis B virus (HBV)-associated HCC ≤3 cm. METHODS A total of 359 patients with single-nodule HBV-associated HCC ≤3 cm treated with curative thermal ablation were retrospectively investigated. Hierarchical cluster analysis was applied to obtain more homogeneous patient clusters concerning demographic and physiological characteristics. Discriminant analysis was performed to identify the relatively important variables for cluster analysis. Multiple correspondence analysis (MCA) was used to clarify the relationship between clusters and categorical variables. Overall survival (OS) was compared among clusters using the Kaplan-Meier model. RESULTS A two-cluster model was identified. Cluster 1 (n = 85) showed a higher percentage of female and older patients, higher inflammation response (higher prognostic nutritional index [PNI] and Glasgow prognostic score [GPS]), worse liver function (higher albumin-bilirubin grade and Child-Pugh grade), and relatively poorer immune status (higher neutrophil-to-lymphocyte ratio [NLR]) than cluster 2 (n = 274). NLR and GPS were the two most influential variables for cluster analysis (p < .0001). Cluster 2 had a significantly better prognosis than cluster 1. MCA revealed a clear negative correlation between inflammation status and liver function. Compared with cluster 1, the hazard ratios for OS of cluster 2 were 0.47 and 0.52 before and after adjusting for age, respectively (p < .05). CONCLUSIONS This study identified two sub-phenotypes of patients with single-nodule HBV-associated HCC ≤3 cm and their association with the outcome of thermal ablation alone as the first-line therapy. Key points Thermal ablation alone as the first-line therapy is not suitable for all patients with single-nodule hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) ≤3 cm. Patients with single-nodule HBV-associated HCC ≤3 cm can be identified as two sub-phenotypes associated with the outcome of thermal ablation alone as the first-line therapy, based on key preoperative clinical characteristics, especially inflammatory response and immune status. Patients with single-nodule HBV-associated HCC ≤3 cm characterized by late-onset disease, worse liver function, poorer immune status, and higher inflammatory response (with higher inflammatory response being the most important factor) are not suitable for thermal ablation alone as the first-line therapy. In contrast, patients with single-nodule HBV-associated HCC ≤3 cm characterized by early-onset disease, better liver function, lower inflammatory response, and good immune status (with lower inflammatory response being the most important factor) are particularly suitable for thermal ablation alone. Implications for patient care In the treatment of patients with single-nodule HBV-associated HCC ≤3 cm, thermal ablation alone as the first-line therapy should be carefully considered after recognizing the key clinical characteristics, among which inflammatory response and immune status are the two most important factors involved in clinical heterogeneity, and inflammatory response is closely related to the prognosis of thermal ablation alone as the first-line therapy for these patients.
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Affiliation(s)
- Shuanggang Chen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ying Wu
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Han Qi
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Lujun Shen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Weimei Ma
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Department of Radiology, The Eighth Affiliated Hospotal, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Fei Cao
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Yuhong Diao
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ting Wang
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Shunling Ou
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Weijun Fan
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
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Motooka K, Morishita K, Ito N, Shinzaki S, Tashiro T, Nojima S, Shimizu K, Date M, Sakata N, Yamada M, Takamatsu S, Kamada Y, Iijima H, Mizushima T, Morii E, Takehara T, Miyoshi E. Detection of fucosylated haptoglobin using the 10-7G antibody as a biomarker for evaluating endoscopic remission in ulcerative colitis. World J Gastroenterol 2021; 27:162-175. [PMID: 33510557 PMCID: PMC7807302 DOI: 10.3748/wjg.v27.i2.162] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 11/11/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation of the digestive tract. Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD, their low sensitivity and high variability characteristics limit clinical efficacy. Thus, the establishment of better biomarkers is expected. Fucosylation is one of the most important glycosylation modifications of proteins. Fucosylated haptoglobin (Fuc-Hpt) is used as a biomarker for several cancers and inflammation-related diseases. We recently established a novel glycan monoclonal antibody (mAb), designated 10-7G, which recognizes Fuc-Hpt. We developed an enzyme-linked immunosorbent assay (ELISA) to measure serum levels of Fuc-Hpt (10-7G values).
AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.
METHODS This was a case control study. Intestinal tissues of IBD patients (n = 10) were examined immunohistochemically using the 10-7G mAb. We determined 10-7G values using serum from patients with ulcerative colitis (UC, n = 110), Crohn’s disease (n = 45), acute enteritis (AE, n = 11), and healthy volunteers (HVs) who exhibited normal (n = 20) or high (n = 79) C-reactive protein (CRP) levels at medical check-up. We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers.
RESULTS In the immunohistochemical analysis, positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles. The 10-7G values were significantly higher in patients with IBD (P < 0.001) and AE (P < 0.05) compared with HVs. In addition, 10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC, particularly the CRP level (rs = 0.525, P = 0.003) and clinical activity index score (rs = 0.435, P = 0.038). However, there was no correlation between 10-7G values and CRP in HVs with high CRP levels, suggesting that the 10-7G values is not the same as a general inflammation biomarker. ROC curve analysis showed that area under the curve (AUC) value of 10-7G values for the diagnosis of endoscopic remission was higher than other biomarkers (AUC value = 0.699).
CONCLUSION The serum 10-7G value is a novel biomarker for evaluating intestinal inflammation and endoscopic mucosal healing in UC.
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Affiliation(s)
- Kei Motooka
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Koichi Morishita
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Nami Ito
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Shinichiro Shinzaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Taku Tashiro
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Satoshi Nojima
- Department of Pathology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Kayoko Shimizu
- FUJIFILM Wako Pure Chemical Corporation, Amagasaki 661-0963, Hyogo, Japan
| | - Mutsuhiro Date
- FUJIFILM Wako Pure Chemical Corporation, Amagasaki 661-0963, Hyogo, Japan
| | - Natsumi Sakata
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Momoko Yamada
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Shinji Takamatsu
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Yoshihiro Kamada
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Hideki Iijima
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
| | - Eiji Miyoshi
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
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Shentova-Eneva R, Velikova T. Laboratory Assessment of Disease Activity in Pediatric Patients with Inflammatory Bowel Disease: What’s New? GASTROENTEROLOGY INSIGHTS 2020; 11:58-71. [DOI: 10.3390/gastroent11020009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Laboratory tests are an integral part of both the diagnostic and follow-up algorithm of patients with inflammatory bowel disease (IBD). Their advantages over other non-invasive methods for assessing disease activity are greater objectivity than clinical activity indices and imaging studies. This review aims to analyze shortly the most common laboratory tests used to assess disease activity in pediatric patients with IBD. In addition to the conventional blood and serum markers that are not specific for gut inflammation, although routinely used, we also reviewed the established fecal markers such as calprotectin, lactoferrin, M2-pyruvate kinase, osteoprotegerin, HMGB1, chitinase 3-like 1, and the promising non-coding microRNA. In conclusion, neither marker is unique to the pediatric IBD. More clinical data are required to assess biomarkers’ full potential for diagnosis, management, and follow-up of pediatric IBD patients.
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Affiliation(s)
- Rayna Shentova-Eneva
- Department of Gastroenterology and Hepatology, Medical Faculty, University Children’s Hospital “Professor Ivan Mitev”, Medical University, 16 Akademik Ivan Evstratiev Geshov Blvd, 1606 Sofia, Bulgaria
| | - Tsvetelina Velikova
- Clinical Immunology, Medical Faculty, University Hospital “Lozenetz,”, Sofia University St. Kliment Ohridski, Kozyak 1 Street, 1407 Sofia, Bulgaria
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Kurowski JA, Achkar JP, Gupta R, Barbur I, Bonfield TL, Worley S, Remer EM, Fiocchi C, Viswanath SE, Kay MH. Adipokine Resistin Levels at Time of Pediatric Crohn Disease Diagnosis Predict Escalation to Biologic Therapy. Inflamm Bowel Dis 2020; 27:1088-1095. [PMID: 32978938 PMCID: PMC8355503 DOI: 10.1093/ibd/izaa250] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Hypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD. METHODS Pediatric patients ages 6 to 20 years were enrolled, and their clinical data and anthropometric measurements were obtained. Adipokine levels were measured at 0, 6, and 12 months after CD diagnosis and baseline in control patients (CP). The VAT volumes were measured by magnetic resonance imaging or computed tomography imaging within 3 months of diagnosis. RESULTS One hundred four patients undergoing colonoscopy were prospectively enrolled: 36 diagnosed with CD and 68 CP. The serum adipokine resistin and plasminogen activator inhibitor (PAI)-1 levels were significantly higher in patients with CD at diagnosis than in CP. The VAT volume was similar between CD and CP. Baseline resistin levels at the time of diagnosis in patients with CD who were escalated to biologics was significantly higher than in those not treated using biologic therapy by 12 months (29.8 ng/mL vs 13.8 ng/mL; P = 0.004). A resistin level of ≥29.8 ng/mL at the time of diagnosis predicted escalation to biologic therapy in the first year after diagnosis with a specificity of 95% (sensitivity = 53%; area under the curve = 0.82; P = 0.015 for model with log-scale). There was a significantly greater reduction in resistin (P = 0.002) and PAI-1 (P = 0.010) at the 12-month follow-up in patients on biologics compared with patients who were not treated using biologics. CONCLUSIONS Serum resistin levels at diagnosis of pediatric CD predict the escalation to biologic therapy at 12 months, independent of VAT volumes. Resistin and PAI-1 levels significantly improved in patients with CD after treatment using biologics compared with those not on biologics. These results suggest the utility of resistin as a predictive biomarker in pediatric CD.
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Affiliation(s)
- Jacob A Kurowski
- Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, United States,Address correspondence to: Jacob A. Kurowski, MD, Cleveland Clinic, Pediatric Gastroenterology, Hepatology, and Nutrition, 9500 Euclid Avenue, Desk R3, Cleveland, OH 44195 ()
| | - Jean-Paul Achkar
- Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, United States
| | - Rishi Gupta
- Pediatric Gastroenterology, University of Rochester, Rochester, New York, United States
| | - Iulia Barbur
- Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
| | - Tracey L Bonfield
- Pediatrics, Case Western Reserve University, Cleveland, Ohio, United States
| | - Sarah Worley
- Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Erick M Remer
- Imaging Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Claudio Fiocchi
- Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Satish E Viswanath
- Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
| | - Marsha H Kay
- Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, United States
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Rajab IM, Hart PC, Potempa LA. How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression. Front Immunol 2020; 11:2126. [PMID: 33013897 PMCID: PMC7511658 DOI: 10.3389/fimmu.2020.02126] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 08/05/2020] [Indexed: 12/22/2022] Open
Abstract
C-reactive protein (CRP) is a widely known, hepatically synthesized protein whose blood levels change rapidly and pronouncedly in response to any tissue damaging event associated with an inflammatory response. The synthesis and secretion of CRP is stimulated by interleukin-6, an early pleiotropic cytokine released by macrophages, endothelial, and other cells that are activated when localized normal tissue structures are compromised by trauma or disease. Serum CRP levels can change rapidly and robustly from 10-100-fold within 6–72 h of any tissue damaging event. Elevated blood levels correlate with the onset and extent of both activated inflammation and the acute phase biochemical response to the tissue insult. Because its functional bioactivity as the prototypic acute phase reactant has eluded clear definition for decades, diagnosticians of various conditions and diseases use CRP blood levels as a simple index for ongoing inflammation. In many pathologies, which involves many different tissues, stages of disease, treatments, and responses to treatments, its interpretive diagnostic value requires a deeper understanding of the localized tissue processes and events that contribute signals which regulate protective or pathological host defense bioactivities. This report presents concepts that describe how local tissue activation events can lead to a non-proteolytic, conformational rearrangement of CRP into a unique isoform with distinctive solubility, antigenicity, binding reactivities and bioactivities from that protein widely known and measured in serum. By describing factors that control the expression, tissue localization, half-life and pro-inflammatory amplification activity of this CRP isoform, a unifying explanation for the diagnostic significance of CRP measurement in disease is advanced.
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Affiliation(s)
- Ibraheem M Rajab
- Roosevelt University College of Pharmacy, Schaumburg, IL, United States
| | - Peter C Hart
- Roosevelt University College of Pharmacy, Schaumburg, IL, United States
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30
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Arouca AB, Meirhaeghe A, Dallongeville J, Moreno LA, Lourenço GJ, Marcos A, Huybrechts I, Manios Y, Lambrinou CP, Gottrand F, Kafatos A, Kersting M, Sjöström M, Widhalm K, Ferrari M, Molnár D, González-Gross M, Forsner M, De Henauw S, Michels N. Interplay between the Mediterranean diet and C-reactive protein genetic polymorphisms towards inflammation in adolescents. Clin Nutr 2020; 39:1919-1926. [PMID: 31500937 DOI: 10.1016/j.clnu.2019.08.016] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 07/20/2019] [Accepted: 08/15/2019] [Indexed: 12/16/2022]
Abstract
AIM From a nutrigenetics perspective, we aim to investigate the moderating role of the Mediterranean diet and each of its subgroups in the association between C-reactive protein (CRP) gene polymorphisms and CRP blood concentration in adolescents. METHODS In 562 adolescents (13-17 y) of the European HELENA study, data was available on circulating CRP levels as inflammatory biomarker, three CRP gene SNPs (rs3093068, rs1204, rs1130864), food intake determined by a self-administered computerized 24 h-dietary recall for 2 days, and body composition. A 9-point Mediterranean diet score and each food subgroup were tested as moderator via SNP*diet interaction. Analyzes were adjusted for age, sex, puberty, adiposity and socioeconomic status. RESULTS The minor allele frequencies of rs3093068 and rs1130864 SNPs (GG and TT, respectively) were associated with higher CRP concentrations, while rs1205 (CT/TT) was associated with lower CRP concentrations. There were significant interactions between rs3093068 and Mediterranean diet (B = -0.1139, p = 0.011), or the fish food subgroup (B = -0.0090, p = 0.022), so that those with the highest genetic CRP risk underwent the highest CRP attenuation by a healthier diet. Although the effect of diet and SNP was substantial, the explained variance by interaction was only 1%. CONCLUSION Greater adherence to the Mediterranean diet and particularly its fish component was associated with a lower CRP blood concentrations especially in those at highest genetic risk due to the rs3093068 SNP.
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Affiliation(s)
- Aline B Arouca
- Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Belgium.
| | - Aline Meirhaeghe
- UMR1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Centre Hosp. Univ Lille, Institut Pasteur de Lille, Université de Lille, Lille, France.
| | - Jean Dallongeville
- UMR1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Centre Hosp. Univ Lille, Institut Pasteur de Lille, Université de Lille, Lille, France.
| | - Luis A Moreno
- GENUD: "Growth, Exercise, Nutrition and Development" Research Group, Facultad de Ciencias de la Salud, University of Zaragoza, Spain; Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
| | - Gustavo Jacob Lourenço
- Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
| | - Ascensión Marcos
- Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Madrid, Spain.
| | - Inge Huybrechts
- Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Belgium; International Agency for Research on Cancer, Lyon, France.
| | - Yannis Manios
- Department of Nutrition and Dietetics, School of Health Science & Education, Harokopio University, Athens, Greece.
| | - Christina-Paulina Lambrinou
- Department of Nutrition and Dietetics, School of Health Science & Education, Harokopio University, Athens, Greece.
| | | | | | - Mathilde Kersting
- Research Department of Child Nutrition, Pediatric University Clinic, Ruhr-University Bochum, Germany.
| | - Michael Sjöström
- Department of Biosciences, Unit for Preventive Nutrition, Karolinska Institutet, Huddinge, Sweden.
| | - Kurt Widhalm
- Department of Gastroenterology and Hepatology, Medical University of Vienna, Austria.
| | - Marika Ferrari
- Research Centre for Food and Nutrition, Council for Agricultural Research and Economics (CREA-AN), Italy.
| | - Denes Molnár
- Department of Pediatrics, Medical School, University of Pécs, Pécs, Hungary.
| | - Marcela González-Gross
- ImFine Research Group, Department of Health and Human Performance, Facultad de Ciencias de la Actividad Física y del Deporte-INEF, Universidad Politécnica de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
| | | | - Stefaan De Henauw
- Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Belgium.
| | - Nathalie Michels
- Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Belgium.
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Wang X, Fan Y, Wang L, Chen B, Lu Y, Luo D. The association between the C-reactive protein gene +1444C/T polymorphism and Parkinson's disease susceptibility in a Chinese population. Gene 2020; 753:144808. [PMID: 32470505 DOI: 10.1016/j.gene.2020.144808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/28/2020] [Accepted: 05/22/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVE C-reactive protein (CRP) is increased in Parkinson's disease (PD). The CRP +1444C/T (rs1130864) polymorphism is located in the 3' untranslated region (3'-UTR) and is associated with serum CRP concentrations. We explored the relationship between the CRP +1444C/T polymorphism and susceptibility to PD. METHODS A total of 1000 subjects from a Chinese population were recruited into this case-control study, including 500 PD patients and 500 healthy controls. The genotype of the CRP +1444C/T polymorphism was tested by Sanger sequencing, and the Hardy-Weinberg equilibrium (HWE) was assessed in the groups. The odds ratios and 95% confidence intervals were calculated to evaluate the strength of any correlations in allelic, dominant, recessive, and additive genetic models. RESULTS The genotypic distribution of the CRP +1444C/T polymorphism was consistent with HWE in controls, and markedly different with cases. The CRP +1444C/T polymorphism was associated with increased PD risk in allelic and dominant models in the overall and male population, but not the female subgroup. CONCLUSION The presence of a CRP +1444C/T polymorphism may be associated with an increased risk of PD in our Chinese population. Given the missing support for a role of this SNP in PD in the pre-existing GWAS, the SNP may not be genuinely associated with PD despite some positive candidate gene studies.
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Affiliation(s)
- Xiong Wang
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Yawei Fan
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Lu Wang
- Key Laboratory of Brain Research of Henan Province, Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003 China
| | - Bo Chen
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yanjun Lu
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Danju Luo
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 China.
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Ayari F, Ben Chaaben A, Ben Ammar H, Nefzi R, Ouni N, Mihoub O, Abaza H, Aissa A, Douik H, Gara S, Larnaout A, Salmi A, Ben Ammar-El Gaaied A, Leboyer M, El Hechmi Z, Guemira F, Tamouza R. Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population. Encephale 2020; 46:241-247. [PMID: 31959465 DOI: 10.1016/j.encep.2019.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 09/23/2019] [Accepted: 10/07/2019] [Indexed: 12/13/2022]
Abstract
The pathogenic mechanisms underlying Schizophrenia (SZ), one of the most frequent mental disorders, are complex and poorly understood. Several evidences suggest that inflammatory processes may underpin some of its neurobiological correlates. The aim of this study was: (i) to analyze the potential association between circulating levels of the C-reactive protein (CRP), a crucial inflammatory marker, and Schizophrenia in Tunisian patients and healthy controls (HC) cohorts; (ii) to investigate the genetic diversity of three CRP variants (rs1417938, rs1130864 and rs1205) and; (iii) to analyze a potential relationship between expression and genetic data and clinical and socio demographical characteristics. CRP polymorphisms were exanimated for 155 patients and 203 HC by taqMan5'-nuclease. High-sensitivity CRP (hs-CRP) serum level was measured in 128 clinically stable out-patient SZ patients and 63 HC subjects via an automated biochemical analyzer. We found that hs-CRP levels were significantly higher in SZ patients as compared to HC. No significant differences were found when the proportions of CRP variants were compared in patients and HC. Further analysis according to clinical and socio demographical characteristics revealed a positive association with age and hypertension. Our data on an original Tunisian sample confirm the previous finding in others population groups.
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Affiliation(s)
- F Ayari
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia.
| | - A Ben Chaaben
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - H Ben Ammar
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - R Nefzi
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - N Ouni
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - O Mihoub
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - H Abaza
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - A Aissa
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - H Douik
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - S Gara
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - A Larnaout
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - A Salmi
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - A Ben Ammar-El Gaaied
- Immunology Department, Faculty of Mathematics, Physics and Natural Sciences, Tunis El Manar University, Tunis, Tunisia
| | - M Leboyer
- Inserm U 955, FondaMental foundation, department of psychiatry, university hospital Mondor, AP-HP, 1006 Créteil, France
| | - Z El Hechmi
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - F Guemira
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - R Tamouza
- Inserm U 955, FondaMental foundation, department of psychiatry, university hospital Mondor, AP-HP, 1006 Créteil, France
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Zhang L, Duan H, Zheng X, Bin P, Zheng Y. C-Reactive Protein Gene Polymorphisms Correlated with Serum CRP Levels of Diesel Engine Exhaust-Exposed Workers. Health (London) 2020. [DOI: 10.4236/health.2020.126047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Evers AK, Veeh J, McNeill R, Reif A, Kittel-Schneider S. C-reactive protein concentration in bipolar disorder: association with genetic variants. Int J Bipolar Disord 2019; 7:26. [PMID: 31788733 PMCID: PMC6885457 DOI: 10.1186/s40345-019-0162-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 10/18/2019] [Indexed: 12/17/2022] Open
Abstract
Background Several recent studies have investigated the role of C-reactive protein (CRP) in bipolar disorder (BD), but few studies have directly investigated the interaction between CRP genetic variants and peripheral CRP concentration across different phases of BD. In this study, we aimed to replicate previous findings that demonstrated altered CRP levels in BD, and to investigate whether there is an association of peripheral protein expression with genetic variants in the CRP gene. Methods 221 patients were included in the study, of which 183 (all episodes, 46 not medicated, 174 medicated) were genotyped for CRP single-nucleotide polymorphisms (SNPs) shown to influence peripheral CRP protein expression (rs1800947, rs2808630, rs1417938, rs1205). Results There were no differences in CRP levels associated with the genotypes, only regarding the rs1205 SNP there were significantly different CRP protein expression between the genotypes when taking body mass index, age, BD polarity, subtype and leukocyte number into account. However, we could show significantly elevated CRP protein expression in manic patients compared to euthymic and depressed patients, independent from genotype. Medication was found to have no effect on CRP protein expression. Conclusions These results indicate that low grade inflammation might play a role in mania and might be rather a state than a trait marker of bipolar disorder.
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Affiliation(s)
- Ann-Kristin Evers
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt Am Main, Germany
| | - Julia Veeh
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt Am Main, Germany
| | - Rhiannon McNeill
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt Am Main, Germany.,Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, University of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany
| | - Andreas Reif
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt Am Main, Germany
| | - Sarah Kittel-Schneider
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt Am Main, Germany. .,Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, University of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.
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35
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The relationship between c-reactive protein gene +1444C/T, 3407T/C polymorphisms and colorectal cancer susceptibility. Gene 2019; 710:145-147. [DOI: 10.1016/j.gene.2019.05.052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/28/2019] [Accepted: 05/25/2019] [Indexed: 01/14/2023]
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Kasapoğlu Aksoy M, Altan L, Görükmez O, Güner A, Ayar K. The relationship between CRP gene polymorphism (rs2794521, rs3091244), ASDAS-CRP and ASDAS-ESR in ankylosing spondylitis. Mod Rheumatol 2019; 30:715-720. [PMID: 31267817 DOI: 10.1080/14397595.2019.1639916] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Background: We aimed to investigate the haplotypes and alleles of two variants (rs2794521 and rs3091244) in AS patients and to examine their relationship with ASDAS-CRP and ASDAS-ESR values.Methods: We evaluated 160 AS patients diagnosed according to the ASAS criteria. ASDAS-CRP and ASDAS-ESR values were calculated. ESR and CRP were examined. The restriction fragment length polymorphism (RFLP) method was used for detecting the rs2794521 and rs3091244 regions on the CRP gene.Results: As a result of the evaluation of rs2794521 gene polymorphism using PCR, TT, TC and CC genotypes were observed in 90, 81 and 9 individuals, respectively. As a result of the evaluation of rs3091244 gene polymorphism, CC, AC and TT genotypes were observed in 104, 51 and 5 individuals, respectively. T allele and C allele were found in rs2794521 gene by 75% and 25%, respectively. In addition, T allele, C allele and A allele were found in rs3091244 gene by 80%, 17% and 3%, respectively. With the help of regression equation, ASDAS-CRP level was 0.34 units higher in cases with rs3091244 C allele than cases without rs3091244 C alleles.Conclusion: CRP rs3091244 C allele may be associated with the increased relative risk for ASDAS-CRP.
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Affiliation(s)
- Meliha Kasapoğlu Aksoy
- Department of Physical Medicine and Rehabilitation, Bursa Yüksek İhtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey
| | - Lale Altan
- Department of Physical Medicine and Rehabilitation, Bursa Yüksek İhtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey.,Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Orhan Görükmez
- Department of Genetics, Bursa Yüksek İhtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey
| | - Altuğ Güner
- Department of Physical Medicine and Rehabilitation, Bursa Yüksek İhtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey
| | - Koray Ayar
- Department of Romatology, Bursa Yüksek İhtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey
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Jebur HB, Masroor M, Ahmad H, Khan NA, Akther J, Bharali D, Singh VK, Verma A, Khan S, Khan V, Hasan R, Bhatt D, Goyal Y, Dev K. CRP Gene Polymorphism and Their Risk Association With Type 2 Diabetes Mellitus. Open Access Maced J Med Sci 2019; 7:33-37. [PMID: 30740156 PMCID: PMC6352458 DOI: 10.3889/oamjms.2019.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 10/18/2018] [Accepted: 10/20/2018] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND: C-reactive protein (CRP) is an inflammatory marker associated with T2DM, obesity, insulin resistance, and cardiovascular disease. AIM: The present study evaluates the association of CRP +1059 G/C polymorphism of the CRP gene in 100 T2D cases and 100 healthy controls. METHODS: Present study was done by allele specific PCR method to study the CRP gene polymorphism in study subjects. RESULTS: Study found that CRP (+1059 G/C) genotype distribution among case and controls was found to be significant (p=0.001), Higher CRP C allele frequency (0.16) was observed compared to controls (0.04). CRP +1059 GC and CC had 2.72 (1.12-6.61), 20.56 (1.16-362.1) risk for T2D. It has been observed, HTN, Obesity, Smoking and alcoholism was found to be associated with increased risk of T2D, and a significant difference was observed in biochemical parameters. CONCLUSION: Study concluded that CRP gene polymorphism was found to be associated with risk of Type 2 Diabetes and risk was linked with heterozygosity and mutant homozygosity. Hypertension, Obesity, Smoking and alcoholism increases the risk of occurrence of Type 2 Diabetes.
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Affiliation(s)
| | - Mirza Masroor
- Deparment of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, India
| | - Hafiz Ahmad
- Department of Medical Microbiology and Immunology, RAK Medical & Health Sciences University, Ras Al Khaimah, UAE
| | - Naushad Ahmad Khan
- Department of Environmental Medicine, University of Rochester, Newyork, USA
| | - Juheb Akther
- Deparment of Pharmacology, Faculty of Medicine, WAIST University, Iraq
| | - Dipu Bharali
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Vijay Kumar Singh
- Department of Biochemistry, Maulana Azad Medical College, New Delhi, India
| | - Amit Verma
- Department of Biotechnology, Jamia Millia Islamia, University, New Delhi, India
| | - Shahbaz Khan
- Department of Biotechnology, Jamia Millia Islamia, University, New Delhi, India
| | - Vasiuddin Khan
- Department of Biotechnology, Jamia Millia Islamia, University, New Delhi, India
| | - Rameez Hasan
- Department of Biotechnology, Jamia Millia Islamia, University, New Delhi, India
| | - Deepti Bhatt
- Department of Biotechnology, Jamia Millia Islamia, University, New Delhi, India
| | - Yamini Goyal
- Department of Biotechnology, Jamia Millia Islamia, University, New Delhi, India
| | - Kapil Dev
- Department of Biotechnology, Jamia Millia Islamia, University, New Delhi, India
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Titz B, Gadaleta RM, Lo Sasso G, Elamin A, Ekroos K, Ivanov NV, Peitsch MC, Hoeng J. Proteomics and Lipidomics in Inflammatory Bowel Disease Research: From Mechanistic Insights to Biomarker Identification. Int J Mol Sci 2018; 19:ijms19092775. [PMID: 30223557 PMCID: PMC6163330 DOI: 10.3390/ijms19092775] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 09/11/2018] [Accepted: 09/12/2018] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) represents a group of progressive disorders characterized by recurrent chronic inflammation of the gut. Ulcerative colitis and Crohn's disease are the major manifestations of IBD. While our understanding of IBD has progressed in recent years, its etiology is far from being fully understood, resulting in suboptimal treatment options. Complementing other biological endpoints, bioanalytical "omics" methods that quantify many biomolecules simultaneously have great potential in the dissection of the complex pathogenesis of IBD. In this review, we focus on the rapidly evolving proteomics and lipidomics technologies and their broad applicability to IBD studies; these range from investigations of immune-regulatory mechanisms and biomarker discovery to studies dissecting host⁻microbiome interactions and the role of intestinal epithelial cells. Future studies can leverage recent advances, including improved analytical methodologies, additional relevant sample types, and integrative multi-omics analyses. Proteomics and lipidomics could effectively accelerate the development of novel targeted treatments and the discovery of complementary biomarkers, enabling continuous monitoring of the treatment response of individual patients; this may allow further refinement of treatment and, ultimately, facilitate a personalized medicine approach to IBD.
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Affiliation(s)
- Bjoern Titz
- PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchatel, Switzerland.
| | - Raffaella M Gadaleta
- PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchatel, Switzerland.
| | - Giuseppe Lo Sasso
- PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchatel, Switzerland.
| | - Ashraf Elamin
- PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchatel, Switzerland.
| | - Kim Ekroos
- Lipidomics Consulting Ltd., Irisviksvägen 31D, 02230 Esbo, Finland.
| | - Nikolai V Ivanov
- PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchatel, Switzerland.
| | - Manuel C Peitsch
- PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchatel, Switzerland.
| | - Julia Hoeng
- PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchatel, Switzerland.
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Kocarnik JM, Richard M, Graff M, Haessler J, Bien S, Carlson C, Carty CL, Reiner AP, Avery CL, Ballantyne CM, LaCroix AZ, Assimes TL, Barbalic M, Pankratz N, Tang W, Tao R, Chen D, Talavera GA, Daviglus ML, Chirinos-Medina DA, Pereira R, Nishimura K, Bůžková P, Best LG, Ambite JL, Cheng I, Crawford DC, Hindorff LA, Fornage M, Heiss G, North KE, Haiman CA, Peters U, Le Marchand L, Kooperberg C. Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study. Hum Mol Genet 2018; 27:2940-2953. [PMID: 29878111 PMCID: PMC6077792 DOI: 10.1093/hmg/ddy211] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 05/02/2018] [Accepted: 05/28/2018] [Indexed: 12/11/2022] Open
Abstract
C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value <2.5E-7. Three loci have no (HACL1, OLFML2B) or only limited (PLA2G6) previous associations with CRP levels. Six loci had different top hits in race/ethnicity-specific versus overall analyses. Fine-mapping refined the signal in six loci, particularly in HNF1A. Conditional analyses provided evidence for secondary signals in LEPR, IL1RN and HNF1A, and for multiple independent signals in CRP and APOE. We identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals at several loci and found evidence for multiple independent signals at several well-known loci. This study demonstrates the benefit of conducting inclusive genetic association studies in large multiethnic populations.
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Affiliation(s)
- Jonathan M Kocarnik
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Institute of Translational Health Sciences, University of Washington, Seattle, WA, USA
| | - Melissa Richard
- Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX, USA
| | - Misa Graff
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
| | - Jeffrey Haessler
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Stephanie Bien
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Chris Carlson
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | | | - Alexander P Reiner
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Christy L Avery
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
| | - Christie M Ballantyne
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
| | - Andrea Z LaCroix
- Department of Epidemiology, University of San Diego, San Diego, CA, USA
| | | | - Maja Barbalic
- Division of Epidemiology, Human Genetics & Environmental Sciences, The University of Texas, Houston, TX, USA
| | - Nathan Pankratz
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Weihong Tang
- Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN, USA
| | - Ran Tao
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Dongquan Chen
- Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Gregory A Talavera
- Division of Health Promotion and Behavioral Science, San Diego State University, San Diego, CA, USA
| | - Martha L Daviglus
- Institute for Minority Health Research, University of Illinois College of Medicine, Chicago, IL, USA
| | - Diana A Chirinos-Medina
- Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Rocio Pereira
- Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Katie Nishimura
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Petra Bůžková
- Department of Biostatistics, University of Washington, Seattle, WA, USA
| | - Lyle G Best
- Missouri Breaks Industries Research, Inc., Eagle Butte, SD, USA
| | - José Luis Ambite
- Information Sciences Institute, University of Southern California, Marina del Rey, CA, USA
| | - Iona Cheng
- Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA
| | - Dana C Crawford
- Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
| | | | - Myriam Fornage
- Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX, USA
- Human Genetics Center, School of Public Health, The University of Texas Health Science Center, Houston, TX, USA
| | - Gerardo Heiss
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
| | - Kari E North
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
| | - Christopher A Haiman
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Ulrike Peters
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | | | - Charles Kooperberg
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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40
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IVKIN АА, GRIGORIEV EV, SHUKEVICH DL. DIAGNOSTICS OF COGNITIVE DYSFUNCTION IN PATIENTS IN THE INTENSIVE CARE WARDS. MESSENGER OF ANESTHESIOLOGY AND RESUSCITATION 2018. [DOI: 10.21292/2078-5658-2018-15-3-47-55] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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41
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Increased C-reactive protein plasma levels are not involved in the onset of post-operative atrial fibrillation. J Cardiol 2017; 70:578-583. [DOI: 10.1016/j.jjcc.2017.03.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 03/06/2017] [Accepted: 03/23/2017] [Indexed: 12/19/2022]
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Cipriani V, Hogg RE, Sofat R, Moore AT, Webster AR, Yates JRW, Fletcher AE. Association of C-Reactive Protein Genetic Polymorphisms With Late Age-Related Macular Degeneration. JAMA Ophthalmol 2017; 135:909-916. [PMID: 28750115 DOI: 10.1001/jamaophthalmol.2017.2191] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Importance C-reactive protein (CRP) is a circulating inflammatory marker associated with late age-related macular degeneration (AMD). It remains uncertain whether the association between CRP concentrations and AMD is causal. Objective To assess whether CRP (OMIM 123260) single-nucleotide polymorphisms that influence circulating CRP concentrations are associated with late AMD. Design, Setting, and Participants Participants in 2 UK, hospital-based, case-control studies (Cambridge AMD study and Moorfields Eye Hospital AMD study) and 1 pan-European, cross-sectional, population-based study (the European Eye [EUREYE] Study) were recruited between November 6, 2000, and April 30, 2007. Participants underwent dilated stereo-digital fundus photography graded according to the International Classification of Age-related Maculopathy and Macular Degeneration. There were 1727 cases of late AMD (1151 neovascular, 384 geographic atrophy, and 192 mixed [neovascular AMD and geographic atrophy]) and 1153 controls. Early AMD cases (n = 574) were included only from the EUREYE Study. Data analysis was performed from August 1 to November 30, 2016. Four common single-nucleotide polymorphisms (rs1205, rs1130864, rs1800947, and rs3093077) were selected based on demonstrated influence on circulating CRP concentrations in the literature. In one study, genotyping of rs3093077 failed, and rs1800947 was typed in only 1 study. Main Outcomes and Measures A genetic multiplicative model was used for the association of single-nucleotide polymorphisms with late AMD adjusted for age and sex. Results Among the 1727 patients with late AMD, the mean (SD) age was 78.7 (7.4) years, and 668 (38.7%) were men. The mean (SD) age of the controls was 74.9 (7.0) years, and 510 (44.2%) were men. In the pooled results of all 3 studies, neither rs1205 (odds ratio [OR], 0.99; 95% CI, 0.86-1.14) nor rs1130864 (OR, 0.96; 95% CI, 0.83-1.11) was associated with late AMD. For geographic atrophy, rs1205 had an OR of 0.91 (95% CI, 0.74-1.13) and rs1130864 had an OR of 0.94 (95% CI, 0.76-1.16). For neovascular AMD, rs1205 had an OR of 1.01 (95% CI, 0.87-1.19) and rs1130864 had an OR of 0.99 (95% CI, 0.84-1.16). There was no association of rs3093077 and rs1800947 with late AMD or any late AMD phenotype. There were no significant findings for early AMD. Conclusions and Relevance Our results do not support a causal association between CRP concentrations and AMD.
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Affiliation(s)
- Valentina Cipriani
- Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, University College London, London, England.,Moorfields Eye Hospital, London, England.,University College London Genetics Institute, London, England
| | - Ruth E Hogg
- Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland
| | - Reecha Sofat
- Centre for Clinical Pharmacology, Division of Medicine, University College London, London, England
| | - Anthony T Moore
- Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, University College London, London, England.,Moorfields Eye Hospital, London, England.,Ophthalmology Department, School of Medicine, University of California, San Francisco
| | - Andrew R Webster
- Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, University College London, London, England.,Moorfields Eye Hospital, London, England
| | - John R W Yates
- Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, University College London, London, England.,Department of Medical Genetics, University of Cambridge, Cambridge, England
| | - Astrid E Fletcher
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England
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Staging the tumor and staging the host: A two centre, two country comparison of systemic inflammatory responses of patients undergoing resection of primary operable colorectal cancer. Am J Surg 2017; 216:458-464. [PMID: 28967380 DOI: 10.1016/j.amjsurg.2017.08.044] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 08/24/2017] [Accepted: 08/30/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND How systemic inflammation-based prognostic scores such as the modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR) differ across populations of patients with colorectal cancer (CRC) remains unknown. The present study examined the mGPS and NLR in patients from United Kingdom (UK) and Japan. METHODS Patients undergoing resection of TNM I-III CRC in two centres in the UK and Japan were included. Differences in clinicopathological characteristics and mGPS (0-CRP≤10 mg/L, 1-CRP>10 mg/L, 2-CRP>10 mg/L, albumin<35 g/L) and NLR (≤5/>5) were examined. RESULTS Patients from UK (n = 581) were more likely to be female, high ASA and BMI, present as an emergency (all P < 0.01) and have higher T stage compared to those from Japan (n = 559). After controlling for differences in tumor and host characteristics, patients from Japan were less likely to be systemically inflamed (OR: mGPS: 0.37, 95%CI 0.27-0.50, P < 0.001; NLR: 0.53, 95%CI 0.35-0.79, P = 0.002). CONCLUSION Systemic inflammatory responses differ between populations with colorectal cancer. Given their prognostic value, reporting of systemic inflammation-based scores should be incorporated into future studies reporting patient outcomes.
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CRP-level-associated polymorphism rs1205 within the CRP gene is associated with 2-hour glucose level: The SAPPHIRe study. Sci Rep 2017; 7:7987. [PMID: 28801571 PMCID: PMC5554245 DOI: 10.1038/s41598-017-08696-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 07/12/2017] [Indexed: 12/19/2022] Open
Abstract
C-reactive protein (CRP) encoded by CRP gene is a reflection of systemic inflammation. Many studies associated CRP level with diabetes and glucose levels, but the association of CRP gene with these traits is unclear. We conducted a cross-sectional study consisting of 945 siblings from 330 families collected by the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) to investigate associations between CRP polymorphisms, circulating CRP, diabetes, and glucose levels. Five single-nucleotide polymorphisms were analyzed: rs3093059, rs2794521, rs1417938, rs1800947, and rs1205. The generalized estimating equation approach was used to deal with correlated data within families. CRP level was positively correlated with diabetes prevalence and levels of fasting and 2-hour glucose (each P < 0.008). Alleles C at rs3093059 and G at rs1205 were associated with elevated CRP level (each P < 1.2 × 10−6). Allele C at rs3093059 was associated with fasting glucose (β = 0.20, P = 0.045) and G at rs1205 was associated with 2-hour glucose (β = 0.46, P = 0.00090) post oral glucose tolerance test, but only the latter passed Bonferroni correction. No polymorphism was associated with diabetes. Since 2-hour glucose is an indicator of glucose tolerance, this study indicated CRP gene is associated with glucose intolerance.
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Akinkugbe AA, Avery CL, Barritt AS, Cole SR, Lerch M, Mayerle J, Offenbacher S, Petersmann A, Nauck M, Völzke H, Slade GD, Heiss G, Kocher T, Holtfreter B. Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study. J Dent Res 2017; 96:1392-1399. [PMID: 28732187 DOI: 10.1177/0022034517720924] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, <30%, ≥30%) with probing pocket depth (PD) ≥4 mm, and NAFLD status was determined using liver ultrasound assessment. Serum CRP levels were assayed at a central laboratory, and single-nucleotide polymorphisms previously identified through genome-wide association studies as robustly associated with serum CRP were combined into a weighted genetic CRP score (wGSCRP). Logistic regression models estimated the association between periodontitis and NAFLD within strata of serum CRP and separately within strata of the wGSCRP. The prevalence of NAFLD was 26.4% (95% confidence interval [CI], 24.6, 28.1) while 17.8% (95% CI, 16.0-19.6) had ≥30% of sites with PD ≥4 mm. Whereas the wGSCRP was not a modifier ( Pinteraction = 0.8) on the multiplicative scale, serum CRP modified the relationship between periodontitis and NAFLD ( Pinteraction = 0.01). The covariate-adjusted prevalence odds ratio of NAFLD comparing participants with ≥30% of sites with PD ≥4 mm to those with no site affected was 2.39 (95% CI, 1.32-4.31) among participants with serum CRP <1 mg/L. The corresponding estimate was 0.97 (95% CI, 0.57-1.66) for participants with serum CRP levels of 1 to 3 mg/L and 1.12 (95% CI, 0.65-1.93) for participants with serum CRP >3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.
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Affiliation(s)
- A A Akinkugbe
- 1 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - C L Avery
- 1 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - A S Barritt
- 2 Department of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - S R Cole
- 1 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - M Lerch
- 3 Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - J Mayerle
- 4 Department of Medicine, Ludwig-Maximilians University, Munich, Germany
| | - S Offenbacher
- 5 Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - A Petersmann
- 6 Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt-University, Greifswald, Germany
| | - M Nauck
- 6 Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt-University, Greifswald, Germany
| | - H Völzke
- 7 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany, and German Center of Diabetes Research, Site Greifswald, Germany
| | - G D Slade
- 8 Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - G Heiss
- 1 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - T Kocher
- 9 Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany
| | - B Holtfreter
- 10 Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany
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Gene-physical activity interactions in lower extremity performance: inflammatory genes CRP, TNF-α, and LTA in community-dwelling elders. Sci Rep 2017; 7:3585. [PMID: 28620227 PMCID: PMC5472589 DOI: 10.1038/s41598-017-03077-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 04/24/2017] [Indexed: 01/06/2023] Open
Abstract
We assessed gene-gene and gene-physical activity interactions of polymorphisms in C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and lymphotoxin α (LTA) genes on lower extremity performance in community-dwelling elders in Taiwan. Five SNPs (rs1205, rs1130864, rs1800947, rs2794520, and rs3093059) of CRP gene, three SNPs (rs909253, rs1041981, and rs2239704) of LTA gene, and three SNPs (rs3093662, rs1800629, and rs1799964) of TNF-α gene of 472 unrelated elders were genotyped. Lower extremity performance included timed up-and-go test (TUG), walking speed, weight-adjusted leg press (waLP), and timed chair stand (TCS). We detected significant interactions between physical activity with CRP rs2794520, rs1205, and rs3093059; LTA rs909253 and rs1041981; and TNF-α rs1799964 for TCS in women after covariate adjustment (all P < 0.05). In men, significant interactions between physical activity with CRP rs2794520, rs1205, and rs3093059; and LTA rs909253 and rs1041981 for TUG; with CRP rs2794520, rs1205, rs1130864, and rs3093059; and LTA rs909253 and rs1041981 for walking speed; and with TNF-α rs3093662 for waLP after covariate adjustment (all P < 0.05). These variants also significantly interacted with physical activity on TCS in women and on walking speed in men. These results show inflammatory genes are involved in lower extremity performance, likely via gene-physical activity interactions.
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Delongui F, Lozovoy MAB, Iriyoda TMV, Costa NT, Stadtlober NP, Alfieri DF, Flauzino T, Dichi I, Simão ANC, Reiche EMV. C-reactive protein +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels. Clin Rheumatol 2017; 36:1779-1788. [DOI: 10.1007/s10067-017-3695-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 04/24/2017] [Accepted: 05/18/2017] [Indexed: 02/02/2023]
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Serum High-Sensitive C-Reactive Protein Level and CRP Genetic Polymorphisms Are Associated with Abdominal Aortic Aneurysm. Ann Vasc Surg 2017; 45:186-192. [PMID: 28549956 DOI: 10.1016/j.avsg.2017.05.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 03/09/2017] [Accepted: 05/04/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Abdominal aortic aneurysm (AAA) development involves an inflammatory process with a potential genetic background. C-reactive protein (CRP) is an acute phase protein and was elevated in patients with AAA. The aim of this study was to investigate the association among serum high-sensitive CRP (hsCRP) concentration, its CRP genetic polymorphisms, and AAA. METHODS Serum hsCRP concentrations and abdominal aorta diameters were measured, and correlation analysis between them was performed in 155 unrelated participants with AAA and 310 non-AAA controls. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1417938, rs1130864, rs1205, rs1800947) were identified via HapMap. Stratification analysis was performed to evaluate the effects of SNPs on the concentration of serum hsCRP. The association between 4 SNPs and AAA was assessed by unconditional logistic regressions. RESULTS Elevated serum hsCRP level was found to be an independent risk factor for AAA (odds ratio [OR] = 3.91, 95% confidence interval [CI]: 2.45, 6.23) after adjustment for confounding factors. Concentrations of serum hsCRP were significant different (P = 0.01) in 4 subgroups derived from participants with abdominal aorta diameter <20 mm, 20-29 mm, 30-54 mm, and ≥55 mm. Stratification analysis revealed there was significant high frequency of elevated hsCRP levels in subjects carrying rs1205-CC genotype compared with those carrying rs1205-TT or CT genotypes (P = 0.004, OR = 2.31, 95% CI: 1.30, 4.11), suggesting that the genotype CC of rs1205 was associated with higher serum hsCRP levels. However, the frequency of rs1205-CC in AAA patients (15.3%) was similar to control subjects (17.6%), and we could not confirm rs1205-CC was the genetic risk factor of AAA (OR = 1.18, 95% CI: 0.69, 2.01). Moreover, we found another CRP polymorphism rs1417938-TT had a significantly higher likelihood of AAA than the AT genotype (OR = 2.07, 95% CI: 1.06, 4.03) for the first time, indicating there was perhaps a role for rs14117938-T polymorphism that correlates with AAA. CONCLUSIONS Serum hsCRP may be related to the presence of AAA and abdominal aorta diameter. Genetic polymorphisms in CRP gene could influence the concentration of serum hsCRP and the likelihood of AAA, but the causal relationship between AAA and CRP should be demonstrated further.
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Kochhar G, Lashner B. Utility of Biomarkers in the Management of Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2017; 15:105-115. [PMID: 28138859 DOI: 10.1007/s11938-017-0129-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OPINION STATEMENT Inflammatory bowel disease (IBD) is comprised of complex clinical and pathological conditions. It runs a chronic course, and proper management requires constant monitoring of disease activity. Recent evidence suggests that subjective patient scores have a poor correlation with disease activity. Endoscopy remains the gold standard for diagnosing and monitoring disease activity. As healthcare is moving towards less costly and less invasive treatments, the need for biomarkers in the management of IBD is evident. Over the last decade, several biomarkers have been found, which may correct the discrepancy between subjective patient scores and the need for endoscopy.
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Affiliation(s)
- Gursimran Kochhar
- Center for Inflammatory Bowel Diseases, Digestive Disease Institute-A31, The Cleveland Clinic Foundation, 9500, Euclid Ave Cleveland, Cleveland, OH, 44195, USA
| | - Bret Lashner
- Center for Inflammatory Bowel Diseases, Digestive Disease Institute-A31, The Cleveland Clinic Foundation, 9500, Euclid Ave Cleveland, Cleveland, OH, 44195, USA.
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Navarro P, de Dios O, Gavela-Pérez T, Soriano-Guillen L, Garcés C. Relationship between polymorphisms in the CRP, LEP and LEPR genes and high sensitivity C-reactive protein levels in Spanish children. ACTA ACUST UNITED AC 2017; 55:1690-1695. [DOI: 10.1515/cclm-2017-0134] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 02/19/2017] [Indexed: 01/19/2023]
Abstract
AbstractBackground:We investigated the association of single nucleotide polymorphisms (SNPs) in the C-reactive protein (Methods:We measured hs-CRP levels in 646 6–8-year-old and 707 12–16-year-old children using a high-sensitivity C-Reactive Protein ELISA kit. Four SNPs in theResults:The four CRP SNPs studied were significantly (p<0.05) associated with hs-CRP levels in both cohorts. Furthermore, two common CRP haplotypes (constructed using the SNPs in order: rs1205, rs1130864, rs1800947, rs2794521) ACGA and GCGG were associated with significantly lower CRP levels (p<0.05) at both ages. The LEPR SNPs rs1137100 (K109R) and rs1137101 (Q223R), and LEP SNP rs7799039 (G2548A) were also associated to hs-CRP levels (p<0.05) in both cohorts.Conclusions:hs-CRP levels in healthy Spanish children, besides being associated to common polymorphisms in the
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