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Heiat M, Javanbakht M, Jafari D, Poudineh M, Heydari F, Sharafi H, Alavian SM. Correlation of IL-10 and IL18 with the development of liver cirrhosis associated with hepatitis B virus infection: A systematic review. Cytokine 2025; 186:156818. [PMID: 39671883 DOI: 10.1016/j.cyto.2024.156818] [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: 07/01/2024] [Revised: 10/02/2024] [Accepted: 11/16/2024] [Indexed: 12/15/2024]
Abstract
BACKGROUND Patients who have been infected with the Hepatitis B virus (HBV) are susceptible to developing liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The objective of this systematic review was to comprehensively scrutinize the existing evidence concerning the association between host genetic polymorphisms and HBV-associated LC. METHODS We searched databases of PubMed, Scopus, and Web of Science for relevant articles published from building databases to 25 October 2023. RESULT We detected 104 relevant articles, relating to 84 individuals genes. Nine genes had the strong evidence of correlation, including IL-10, IL-18, IL-1B, TGF- β, TLR3, STAT4, IL-1RN, Tim3, and IFN receptors. A positive correlation was found for 33 genes but this data had not yet been replicated, 11 genes had limited or mixed evidence of a correlation, and 34 genes indicated no correlation. IL-10 and IL-18 had the most evidence of correlation. There was a notable amount of diversity in both the design and method of studies and data quality. CONCLUSION IL-10 and IL-18 had the most evidence of correlation. There was a notable amount of diversity in both the design and method of studies and data quality. It is of necessary to take into account the fundamental mechanism behind these associations and discern those that are confounded by the coexistence of other LC/HCC risk factors and response to therapy. These results are expected to guide future studies on the genetic susceptibility of HBV-related LC/HCC.
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Affiliation(s)
- Mohammad Heiat
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Mohammad Javanbakht
- Nephrology and Urology Research Center, Clinical Science Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Davood Jafari
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohadeseh Poudineh
- Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Fatemeh Heydari
- Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Zolotareva K, Dotsenko PA, Podkolodnyy N, Ivanov R, Makarova AL, Chadaeva I, Bogomolov A, Demenkov PS, Ivanisenko V, Oshchepkov D, Ponomarenko M. Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma. Int J Mol Sci 2024; 25:12802. [PMID: 39684516 DOI: 10.3390/ijms252312802] [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: 09/30/2024] [Revised: 11/20/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes' promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services-PANTHER, DAVID, STRING, MetaScape, and GeneMANIA-as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.
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Affiliation(s)
- Karina Zolotareva
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Polina A Dotsenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Nikolay Podkolodnyy
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Institute of Computational Mathematics and Mathematical Geophysics, SB RAS, Novosibirsk 630090, Russia
| | - Roman Ivanov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
| | - Aelita-Luiza Makarova
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
| | - Irina Chadaeva
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Anton Bogomolov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Pavel S Demenkov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Vladimir Ivanisenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Dmitry Oshchepkov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Mikhail Ponomarenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
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Park S, Liu M, Huang S. Association of Polygenic Variants Involved in Immunity and Inflammation with Duodenal Ulcer Risk and Their Interaction with Irregular Eating Habits. Nutrients 2023; 15:nu15020296. [PMID: 36678166 PMCID: PMC9863374 DOI: 10.3390/nu15020296] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/01/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
Genetic and environmental factors are associated with developing and progressing duodenal ulcer (DU) risk. However, the exact nature of the disease pathophysiology and the single nucleotide polymorphism (SNP)-lifestyle interaction has yet to be determined. The purpose of the present study was to examine the SNPs linked to DU risk and their interaction with lifestyles and diets in a large hospital-based cohort of Asians. Based on an earlier diagnosis, the participants were divided into the DU (case; n = 1088) and non-DU (control, n = 56,713) groups. The SNP associated with DU risk were obtained from a genome-wide association study (GWAS), and those promoted genetic impact with SNP-SNP interactions were identified with generalized multifactor dimensionality reduction analysis. The interaction between polygenic risk score (PRS) calculated from the selected genetic variants and nutrient were examined. They were related to actin modification, immune response, and cell migration by modulating leucine-rich repeats (LRR) domain binding, Shaffer interferon regulatory factor 4 (IRF4) targets in myeloma vs. mature B lymphocyte, and Reactome runt-related transcription factor 3 (RUNX3). Among the selected SNPs, rs11230563 (R225W) showed missense mutation and low binding affinity with different food components in the autodock analysis. Glycyrrhizin, physalin B, janthitrem F, and casuarinin lowered it in only wild CD6 protein but not in mutated CD6. Plastoquinone 8, solamargine, saponin D, and matesaponin 2 decreased energy binding affinity in mutated CD6 proteins. The PRS of the 5-SNP and 6-SNP models exhibited a positive association with DU risk (OR = 3.14). The PRS of the 5-SNP PRS model interacted with irregular eating habits and smoking status. In participants with irregular eating habits or smokers, DU incidence was much higher in the participants with high PRS than in those with low PRS. In conclusion, the genetic impact of DU risk was mainly in regulating immunity, inflammation, and actin modification. Adults who are genetically susceptible to DU need to eat regularly and to be non-smokers. The results could be applied to personalize nutrition.
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Affiliation(s)
- Sunmin Park
- Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea
- Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea
- Correspondence: ; Tel.: +82-41-540-5345
| | - Meiling Liu
- Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea
| | - Shaokai Huang
- Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea
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Nath AN, Retnakumar RJ, Francis A, Chhetri P, Thapa N, Chattopadhyay S. Peptic Ulcer and Gastric Cancer: Is It All in the Complex Host-Microbiome Interplay That Is Encoded in the Genomes of "Us" and "Them"? Front Microbiol 2022; 13:835313. [PMID: 35547123 PMCID: PMC9083406 DOI: 10.3389/fmicb.2022.835313] [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: 12/14/2021] [Accepted: 03/18/2022] [Indexed: 11/13/2022] Open
Abstract
It is increasingly being recognized that severe gastroduodenal diseases such as peptic ulcer and gastric cancer are not just the outcomes of Helicobacter pylori infection in the stomach. Rather, both diseases develop and progress due to the perfect storms created by a combination of multiple factors such as the expression of different H. pylori virulence proteins, consequent human immune responses, and dysbiosis in gastrointestinal microbiomes. In this mini review, we have discussed how the genomes of H. pylori and other gastrointestinal microbes as well as the genomes of different human populations encode complex and variable virulome–immunome interplay, which influences gastroduodenal health. The heterogeneities that are encrypted in the genomes of different human populations and in the genomes of their respective resident microbes partly explain the inconsistencies in clinical outcomes among the H. pylori-infected people.
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Affiliation(s)
- Angitha N Nath
- Rajiv Gandhi Centre for Biotechnology, Trivandrum, India
| | - R J Retnakumar
- Rajiv Gandhi Centre for Biotechnology, Trivandrum, India.,Manipal Academy of Higher Education, Manipal, India
| | - Ashik Francis
- Rajiv Gandhi Centre for Biotechnology, Trivandrum, India
| | - Prakash Chhetri
- Department of Zoology, Biotech Hub, Nar Bahadur Bhandari Degree College, Tadong, India
| | - Namrata Thapa
- Department of Zoology, Biotech Hub, Nar Bahadur Bhandari Degree College, Tadong, India
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Osadchuk AM, Davydkin IL, Gricenko TA, Osadchuk MA. [General and particular issues of etiopathogenesis of peptic ulcer and gastric cancer: current status of the problem]. TERAPEVT ARKH 2020; 92:97-103. [PMID: 32598726 DOI: 10.26442/00403660.2020.02.000485] [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: 04/26/2020] [Indexed: 12/16/2022]
Abstract
The development of peptic ulcer (PU) and gastric cancer (GC) is the result of the interaction of various internal and external factors. Moreover, if the role ofHelicobacter pylori(H. pylori) in the development of diseases of the stomach is fully established, the significance of many other factors continues to be discussed. Serious controversy is caused by the participation of various strains ofH. pyloriin the development of PU and GC. First of all, these are Vac- and Cag-positive strains ofH. pylori. The role of genetic human polymorphism in the development of this pathology is debatable. Especially the interleukin genes and necrotizing tumor factor alpha. The role of environmental factors in the formation of PU and GC is not fully understood. So, the role of alcohol, occupational hazards and drugs in the development of these diseases continues to be discussed. Further study of risk factors for various diseases of the stomach will optimize their prevention and treatment. The review presents a modern view of individual issues in the pathogenesis of PU and GC.
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Affiliation(s)
| | | | | | - M A Osadchuk
- Sechenov First Moscow State Medical University (Sechenov University)
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Ren HY, Wen LS, Geng YH, Huang JB, Liu JF, Shen DY, Meng JR. Association between IL-1B gene polymorphisms and Helicobacter pylori infection: A meta-analysis. Microb Pathog 2019; 137:103769. [PMID: 31580959 DOI: 10.1016/j.micpath.2019.103769] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/08/2019] [Accepted: 09/30/2019] [Indexed: 01/10/2023]
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Barseem NF, Khattab ESAEH, Mahasab MM. IL-1β-31/IL1-RA genetic markers association with idiopathic generalized epilepsy and treatment response in a cohort of Egyptian population. Int J Neurosci 2019; 130:348-354. [PMID: 31698971 DOI: 10.1080/00207454.2019.1688809] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Background: Neuroinflammation is an important feature of epileptogenesis.Objectives: To investigate the association of Interleukin-1beta-31 (IL-1β-31) and Interleukin-1 receptor antagonist (IL1-RA) genetic polymorphisms with idiopathic generalized epilepsy and demonstrate their influence on drug resistance in children.Materials and Methods: One hundred children with idiopathic generalized epilepsy were age and gender-matched with apparently healthy controls. Both groups were genotyped for IL-1β-31, and IL1-RA gene variants, analysis of these single nucleotide polymorphisms (SNPs) was done through restriction digestion of the corresponding polymerase chain reaction (PCR) products by restriction fragment length polymorphism (RFLP) assay.Results: Genotype frequency of rs1143627 TT of IL-1β-31 and the homozygous IL1RN*I were found to be more prevalent in epileptic patients (p < .05, OR 0.12 and 5.27respectively). Also observed, T allele of IL-1β-31 and IL1-RAI/I were substantially positively correlated with drug resistance against those who responded well to antiepileptic drugs (AEDs).Conclusions: The significant association with IL-1β-31T and IL1-RAN*I alleles potentiated their useful role as predictive markers for the development of epilepsy and response to medical therapy.
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Affiliation(s)
- Naglaa Fathy Barseem
- Genetic and Endocrinology Unit, Department of Pediatric, Menoufia University, Shebeen Elkom, Egypt
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8
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Abstract
The rapidly declining prevalence of Helicobacter pylori infection and widespread use of potent anti-secretory drugs means peptic ulcer disease has become substantially less prevalent than it was two decades ago. Management has, however, become more challenging than ever because of the threat of increasing antimicrobial resistance worldwide and widespread use of complex anti-thrombotic therapy in the ageing population. Peptic ulcers not associated with H pylori infection or the use of non-steroidal anti-inflammatory drugs are now also imposing substantial diagnostic and therapeutic challenges. This Seminar aims to provide a balanced overview of the latest advances in the pathogenetic mechanisms of peptic ulcers, guidelines on therapies targeting H pylori infection, approaches to treatment of peptic ulcer complications associated with anti-inflammatory analgesics and anti-thrombotic agents, and the unmet needs in terms of our knowledge and management of this increasingly challenging condition.
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Affiliation(s)
- Angel Lanas
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, University of Zaragoza, IIS Aragón, CIBEREHD, Zaragoza, Spain.
| | - Francis K L Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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Ma J, Wu D, Hu X, Li J, Cao M, Dong W. Associations between cytokine gene polymorphisms and susceptibility to Helicobacter pylori infection and Helicobacter pylori related gastric cancer, peptic ulcer disease: A meta-analysis. PLoS One 2017; 12:e0176463. [PMID: 28453551 PMCID: PMC5409176 DOI: 10.1371/journal.pone.0176463] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 04/11/2017] [Indexed: 12/20/2022] Open
Abstract
Objectives The aim of this study is to clarify the associations between IL-1B31C/T, IL-1B-511C/T, IL-8-251T/A gene polymorphisms and the risk of Helicobacter pylori (H. pylori) infection together with H. pylori-related gastric cancer (GC), peptic ulcer disease (PUD). Methods All eligible literature published up to July 2016 were identified by searching Pubmed, Embase, Web of Science and CNKI. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using a fixed or random effects model. Results 29 case-control studies were eligible, and each of them may focus on more than one gene polymorphism. Ultimately, there were 21 studies (3159 cases and 2816 controls) for IL-1B-31C/T, 16 studies (2486 cases and 1989 controls) for IL-1B-511C/T polymorphisms, 9 studies (1963 cases and 1205 controls) for IL-8-251T/A polymorphisms. Overall, an increased risk of H. pylori infection was found for IL-1B-31C/T polymorphisms in total population [OR = 1.134, 95%CI = 1.008–1.275 for recessive model; OR = 1.145, 95%CI = 1.007–1.301 for TT vs CC model]. While, for IL-1B-511C/T and IL8-251T/A polymorphisms, no evidence indicated that they were associated with the risk of H. pylori infection in all genetic models. Furthermore, we found an increased risk of H. pylori-related GC with IL-1B-511C/T polymorphisms [OR = 1.784, 95%CI = 1.289–2.469 for recessive model; OR = 1.772, 95%CI = 1.210–2.594 for TT vs CC model] and IL8-251A/T polymorphisms [OR = 1.810, 95%CI = 1.229–2.667 for recessive model; OR = 1.717, 95%CI = 1.143–2.580 for TT vs AA model], an increased risk of H. pylori-related PUD with IL8-251T/A polymorphisms [OR = 1.364, 95%CI = 1.010–1.843 for recessive model; OR = 1.427, 95%CI = 1.039–1.959 for AA vs TT model]. Conclusions IL-1B-31C/T gene polymorphisms might increase H. pylori infection risk. IL-1B-511-C/T and IL-8-251T/A gene polymorphisms might act as a risk factor to H. pylori-related diseases including GC or PUD
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Affiliation(s)
- Jingjing Ma
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Dandan Wu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Xue Hu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Jiao Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Mingwei Cao
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Weiguo Dong
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
- * E-mail:
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Zhang J, Sun X, Wang J, Zhang F, Li X, Han J. Association of the IL-1RN variable number of tandem repeat polymorphism and Helicobacter pylori infection: A meta-analysis. PLoS One 2017; 12:e0175052. [PMID: 28384207 PMCID: PMC5383105 DOI: 10.1371/journal.pone.0175052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 03/20/2017] [Indexed: 12/12/2022] Open
Abstract
The aim of this study was to clarify the association of IL-1RN variable number of tandem repeat (VNTR) polymorphism and H. pylori infection. We performed a meta-analysis of studies retrieved by systematic searches of Pubmed, Embase and the Cochrane Library. Data were analyzed with STATA 13.1 using pooled odds ratios (ORs) with 95% confidence intervals (CIs). A total of 18 studies were included in our meta-analysis, and IL-1RN VNTR was found to be significantly associated with H. pylori infection in the comparisons of 22+2L vs. LL (OR = 1.17, 95% CI = 1.02-1.33) and 2 allele vs. L allele (OR = 1.18, 95% CI = 1.00-1.40). Stratified analyses on study designs and ethnicities were also conducted. IL-1RN VNTR was positively correlated with H. pylori infection in Asian subgroup and Hospital-Based subgroup (i.e., study samples obtained from hospital inpatients). In conclusion, our study demonstrated that IL-1RN VNTR polymorphism might increase the risk of H. pylori infection, especially in Asians.
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Affiliation(s)
- Jinhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou, China
- Department of Medicine, School of Second Clinical Medicine, Northwest University for Nationalities, Lanzhou, China
- * E-mail: (JH); (JHZ)
| | - Xudong Sun
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Jiemin Wang
- Department of Gastroenterology, Liangzhou Hospital, Wuwei, China
| | - Fuhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou, China
- Department of Medicine, School of Second Clinical Medicine, Northwest University for Nationalities, Lanzhou, China
| | - Xiaohua Li
- Department of Gastroenterology, Liangzhou Hospital, Wuwei, China
| | - Jian Han
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- * E-mail: (JH); (JHZ)
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Zabaglia LM, Rays MS, de Labio RW, Neto AC, Payão SLM, Rasmussen LT. Association between interleukin-1β polymorphisms and gastric disease in children: A correlation with Helicobacter pylori. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2016. [DOI: 10.1016/s2222-1808(16)61117-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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12
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Nishida Y, Hara M, Sakamoto T, Shinchi K, Kawai S, Naito M, Hamajima N, Kadota A, Suzuki S, Ibusuki R, Hirata A, Yamaguchi M, Kuriyama N, Oze I, Mikami H, Kubo M, Tanaka H. Influence of cigarette smoking and inflammatory gene polymorphisms on glycated hemoglobin in the Japanese general population. Prev Med Rep 2016; 3:288-95. [PMID: 27419029 PMCID: PMC4929182 DOI: 10.1016/j.pmedr.2016.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 01/09/2016] [Accepted: 03/11/2016] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE Inflammation is closely involved in the development of type 2 diabetes, and cigarette smoking acts as potent inducer of inflammation. We therefore investigated interactions between inflammation-related gene polymorphisms and cigarette smoking on glycated hemoglobin (HbA1c) in the Japanese general population. METHOD We conducted a cross-sectional study using data collected from 2619 Japanese (1274 males and 1345 females) 40-69 years of age who participated in baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study (2005-2008). Eight polymorphisms in seven genes (interleukin [IL]-1β, IL-2, IL-4, IL-8, IL-10, IL-13 and tumor necrosis factor-α) were determined using the Invader assay. The interactions of smoking and gene polymorphisms on HbA1c levels were analyzed using multiple linear and logistic regression models and analysis of covariance with adjustment for potential confounders. RESULTS Among the eight polymorphisms, only one significant interaction was detected for IL-1β T-31C (P < 0.0001). Among the subjects carrying TT genotype, current heavy smokers (≥ 20 cigarettes/day) had higher HbA1c (5.83 [95% confidence interval 5.67-5.99] %) versus all other smoking status groups (never 5.49 [5.41-5.56] %, former 5.54 [5.43-5.65] %, current moderate [< 20 cigarettes/day] 5.50 [5.30-5.69] %), whereas such differences were not observed in the subjects with C allele. The logistic regression analyses regarding high-normal HbA1c levels showed a similar pattern of results. CONCLUSION Smoking status did not interact with any other inflammation-related polymorphisms except for IL-1β T-31C. Heavy smokers harboring the TT genotype of IL-1β T-31C polymorphism show a greater adverse effect of smoking on HbA1c levels among Japanese middle-aged subjects.
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Affiliation(s)
- Yuichiro Nishida
- Department of Preventive Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Megumi Hara
- Department of Preventive Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Tatsuhiko Sakamoto
- Tosu Public Health and Welfare Office, Saga Prefectural Government, 1234-1 Moto-machi, Tosu 841-0051, Japan
| | - Koichi Shinchi
- Division of International Health and Nursing, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Sayo Kawai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Mariko Naito
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Nobuyuki Hamajima
- Department of Healthcare Administration, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Aya Kadota
- Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Setatsukinowa-cho, Otsu 520-2192, Japan
| | - Sadao Suzuki
- Department of Public Health, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
| | - Rie Ibusuki
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Science, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
| | - Akie Hirata
- Department of Geriatric Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maedashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Miwa Yamaguchi
- Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Nagato Kuriyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachidori Hirokojiagaru, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Isao Oze
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
| | - Haruo Mikami
- Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717, Japan
| | - Michiaki Kubo
- Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan
| | - Hideo Tanaka
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
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Pachathundikandi SK, Müller A, Backert S. Inflammasome Activation by Helicobacter pylori and Its Implications for Persistence and Immunity. Curr Top Microbiol Immunol 2016; 397:117-31. [DOI: 10.1007/978-3-319-41171-2_6] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Hudler P. Challenges of deciphering gastric cancer heterogeneity. World J Gastroenterol 2015; 21:10510-10527. [PMID: 26457012 PMCID: PMC4588074 DOI: 10.3748/wjg.v21.i37.10510] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 06/19/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively.
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Tumor necrosis factor-α and interleukin-1β gene polymorphisms and risk of brain abscess in North Indian population. Cytokine 2015; 75:159-64. [DOI: 10.1016/j.cyto.2015.07.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 07/07/2015] [Accepted: 07/08/2015] [Indexed: 12/30/2022]
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Sun X, Xu Y, Zhang F, Jing T, Han J, Zhang J. Association between the IL1B -31C > T polymorphism and Helicobacter pylori infection in Asian and Latin American population: A meta-analysis. Microb Pathog 2015; 86:45-52. [PMID: 26188264 DOI: 10.1016/j.micpath.2015.07.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 07/11/2015] [Accepted: 07/13/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Host genetic factors that control the production of cytokines, including interleukin-1β (IL-1β), possibly affect susceptibility to many Helicobacter pylori-related diseases. There is a complex interplay between H. pylori infection, the subsequent production of certain cytokines, and H. pylori-related diseases. We conducted a meta-analysis to clarify the association between the IL1B -31C > T polymorphism and H. pylori infection, and possible subsequent pathogenic mechanisms. METHODS Published literature contained within PubMed, Embase, and the Cochrane Library was used in our meta-analysis. Data were analyzed with the STATA 13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Egger's regression test, Begg's rank correlation test, and Begg's funnel plot were used to test publication bias. RESULTS A total of 12 case-control studies comprising 5827 subjects (3335 cases and 2492 controls) were available for our meta-analysis. The IL1B -31C > T polymorphism was associated with an increased risk of H. pylori infection in Asian and Latin American population (TT + CT vs. CC, OR = 1.29, 95% CI = 1.14-1.46; TT vs. CT + CC, OR = 1.23, 95% CI = 1.09-1.39; TT vs. CC, OR = 1.43, 95% CI = 1.22-1.67; T allele vs. C allele, OR = 1.19, 95% CI = 1.10-1.29). A significant association was also found for all genetic models in various subgroups (cancer and no-cancer, hospital- and population-based). CONCLUSION Our meta-analysis demonstrated that IL1B -31C > T polymorphism might increase H. pylori infection risk in Asian and Latin American population. Further studies with different ethnicities and larger sample size are required to validate this result.
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Affiliation(s)
- Xudong Sun
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Yuanyuan Xu
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Fuhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou 730000, China
| | - Tao Jing
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Jian Han
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
| | - Jinhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou 730000, China.
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Datta De D, Roychoudhury S. To be or not to be: The host genetic factor and beyond in Helicobacter pylori mediated gastro-duodenal diseases. World J Gastroenterol 2015; 21:2883-2895. [PMID: 25780285 PMCID: PMC4356907 DOI: 10.3748/wjg.v21.i10.2883] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Revised: 08/28/2014] [Accepted: 01/08/2015] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) have long been associated with a spectrum of disease outcomes in the gastro-duodenal system. Heterogeneity in bacterial virulence factors or strains is not enough to explain the divergent disease phenotypes manifested by the infection. This review focuses on host genetic factors that are involved during infection and eventually are thought to influence the disease phenotype. We have summarized the different host genes that have been investigated for association studies in H. pylori mediated duodenal ulcer or gastric cancer. We discuss that as the bacteria co-evolved with the host; these host gene also show much variation across different ethnic population. We illustrate the allelic distribution of interleukin-1B, across different population which is one of the most popular candidate gene studied with respect to H. pylori infections. Further, we highlight that several polymorphisms in the pathway gene can by itself or collectively affect the acid secretion pathway axis (gastrin: somatostatin) thereby resulting in a spectrum of disease phenotype
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Yamaoka Y, Miftahussurur M. Helicobacter pylori virulence genes and host genetic polymorphisms as risk factors for peptic ulcer disease. Expert Rev Gastroenterol Hepatol 2015; 9:1535-47. [PMID: 26470920 PMCID: PMC5332543 DOI: 10.1586/17474124.2015.1095089] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Helicobacter pylori infection plays an important role in the pathogenesis of peptic ulcer disease (PUD). Several factors have been proposed as possible H. pylori virulence determinants; for example, bacterial adhesins and gastric inflammation factors are associated with an increased risk of PUD. However, differences in bacterial virulence factors alone cannot explain the opposite ends of the PUD disease spectrum, that is duodenal and gastric ulcers; presumably, both bacterial and host factors contribute to the differential response. Carriers of the high-producer alleles of the pro-inflammatory cytokines IL-1B, IL-6, IL-8, IL-10, and TNF-α who also carry low-producer allele of anti-inflammatory cytokines have severe gastric mucosal inflammation, whereas carriers of the alternative alleles have mild inflammation. Recent reports have suggested that the PSCA and CYP2C19 ultra-rapid metabolizer genotypes are also associated with PUD.
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Affiliation(s)
- Yoshio Yamaoka
- Oita University, Baylor College of Medicine Houston United States
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Kim J, Kim Y, Lee KA. Ethnic differences in gastric cancer genetic susceptibility: Allele flips of interleukin gene. World J Gastroenterol 2014; 20:4558-4565. [PMID: 24782608 PMCID: PMC4000492 DOI: 10.3748/wjg.v20.i16.4558] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/12/2013] [Accepted: 03/10/2014] [Indexed: 02/06/2023] Open
Abstract
Polymorphisms in promoter regions of inflammatory cytokines have been widely studied, and potentially functional polymorphisms have been discovered. Conflicting results from meta-analyses of interleukin (IL)-1B and IL-10 polymorphisms show differences in gastric cancer susceptibilities between Caucasian and Asian populations. In particular, we note the suggestion of an allele flip in IL-1B and IL-10 gene polymorphisms. In Asian populations, the IL-1B-1464G/-511C/-31T haplotype indicates risk for gastric cancer, while the opposite haplotype, IL-1B-1464C/-511T/-31C is the risk-related allele in Caucasians. Furthermore, while IL-10-1082G/-819C/-592C is associated with gastric cancer in Asians, IL-10-1082A/-819T/-592T is linked to gastric cancer risk in Caucasians. These seemingly contradictory results may be attributed to distinct carcinogenic mechanisms underlying the different gastric cancer subtypes. The allele flip observed in IL-10 and gastric cancer appears to reflect allelic heterogeneity, similar to that observed in IL-1B. In this review, we focus on the allele flip phenomenon observed between different ethnic groups in an effort to resolve certain controversial results from recent studies on interleukin polymorphism. In addition, we re-emphasize the importance of stratifying gastric cancer subtypes based on anatomical site and Lauren classification to prevent false associations arising through dilution of true ones.
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20
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Biswas A, Panigrahi R, Pal M, De BK, Chakrabarti S, Ghosh MK, Chandra Seth BC, Roychowdhury S, Chakravarty R. Association of Interleukin-1β and Gene Polymorphisms with Liver Pathogenesis in Hepatitis B Virus Infection among Eastern Indian Population. J Clin Exp Hepatol 2013; 3:281-7. [PMID: 25755515 PMCID: PMC3940093 DOI: 10.1016/j.jceh.2013.11.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2013] [Accepted: 11/11/2013] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Interleukin-1β (IL-1β) is an important member of the family of the proinflammatory cytokines that modulate outcome of hepatitis B virus (HBV) infection. OBJECTIVES This study was designed to investigate the relationship between the polymorphic genotypes of the interleukin-1β (IL-1β) promoter region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease outcome in HBV-infected individuals. METHODS DNA was extracted from 395 study subjects including HBV carriers with varying clinical presentations, as well as healthy controls and spontaneously recovered cases (SRC). Polymorphisms in IL-1β (at position -511) and IL-1RN (variable nucleotide tandem repeats, VNTR) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR based assay respectively. RESULTS Among the study subjects, different IL-1β (at position -511) (CC, CT and TT) and IL-1RN (1/1, 1/2, 2/2 and 1/3) polymorphic genotypes were found at variable proportions. Logistic regression analysis revealed, no notable difference at the level of IL-1β promoter (P = 0.244; OR = 0.78; 95% CI = 0.52-1.18) or IL-1RN genotype polymorphism (P = 0.840; OR = 1.03; 95% CI = 0.78-1.36) among the HBV carriers and controls or SRC cases. Pairwise proportion testing showed, IL-1β -511 genotype CC was significantly higher among asymptomatic carriers (ASC) in comparison with liver cirrhosis (LC) patients (P value = 0.028) and healthy control group (P-value = 0.036). IL-1RN genotype 2/2 was considerably higher in LC group than SRC as well as control group. Combinations of IL-1β (-511) and IL-1RN polymorphisms were associated with disease progression, such as CC-1/2 with ASC and TT-2/2 with LC. CONCLUSION IL-1β polymorphisms are found to be associated with disease severity. Different polymorphic combinations are associated with degree of disease severity. Overall this is the first report from Eastern India, which shows association of IL-1β polymorphisms with HBV-related hepatic complications.
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Key Words
- ASC, asymptomatic carriers
- CLD, chronic liver disease
- Eastern India
- HBV
- HBV, hepatitis B virus
- HCC, hepatocellular carcinoma
- IL-1RN, interleukin-1 receptor antagonist gene
- IL-1β, interleukin-1β
- LC, liver cirrhosis
- LR, logistic regression
- PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism
- SNP, single nucleotide polymorphisms
- SRC, spontaneously recovered cases
- USG, ultrasonography
- VNTR, variable nucleotide tandem repeats
- cirrhosis
- interleukin polymorphisms
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Affiliation(s)
- Avik Biswas
- ICMR Virus Unit Kolkata, ID & BG Hospital Campus, Kolkata, India
| | - Rajesh Panigrahi
- Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, USA
| | - Manisha Pal
- Department of Statistics, University of Calcutta, Kolkata, India
| | - Binay K. De
- Department of Medicine, Calcutta Medical College, Kolkata, India
| | | | | | | | | | - Runu Chakravarty
- ICMR Virus Unit Kolkata, ID & BG Hospital Campus, Kolkata, India,Address for correspondence: Runu Chakravarty, ICMR Virus Unit Kolkata, GB 4, 1st Floor, ID & BG Hospital Campus, 57, Dr. Suresh Chandra Banerjee Road, Kolkata 700010, India. Tel.: +91 33 2353 7425; fax: +91 33 2353 7424.
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Zhang BB, Li Y, Feng JQ, Bian DL, Gao XM, Ran MY. No association between IL-1RN VNTR and the risk of duodenal ulcer: A meta-analysis. Hum Immunol 2013; 74:1170-8. [PMID: 23800434 DOI: 10.1016/j.humimm.2013.06.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2013] [Revised: 05/12/2013] [Accepted: 06/14/2013] [Indexed: 12/24/2022]
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Zhang BB, Wang J, Bian DL, Chen XY. No association between IL-1β -31 C/T polymorphism and the risk of duodenal ulcer: a meta-analysis of 3793 subjects. Hum Immunol 2012; 73:1200-6. [PMID: 22917539 DOI: 10.1016/j.humimm.2012.08.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Revised: 07/24/2012] [Accepted: 08/09/2012] [Indexed: 12/11/2022]
Abstract
The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β -31 C/T polymorphism and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 12 studies including 1151 cases and 2642 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β -31 C/T polymorphism and DU (allelic model: OR=0.96, 95%CI=0.86-1.07; additive model: OR=0.85, 95%CI=0.67-1.07; dominant model: OR=0.95, 95%CI=0.81-1.13; and recessive model: OR=0.95, 95%CI=0.79-1.15). Significant association was found in additive model for PB subgroup (OR=0.65, 95%CI=0.44-0.96) and recessive model for non-Asian subgroup (OR=0.72, 95%CI=0.52-0.99). In conclusion, our meta-analysis suggested that there was no evidence of significant association between IL-1β -31 C/T polymorphism and DU with or without Helicobacter pylori infection in overall population, whereas significant association was found by subgroup analyses which showed protective effect of C/C genotype against DU risk.
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Affiliation(s)
- Bei-Bei Zhang
- Department of Medical Affairs, General Hospital of PLA Chengdu Military Area Command, Chengdu 610083, PR China.
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No association between IL-1β -511 C/T polymorphism and the risk of duodenal ulcer: a meta-analysis of 4667 subjects. Gene 2012; 506:188-94. [PMID: 22759516 DOI: 10.1016/j.gene.2012.06.058] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2012] [Accepted: 06/19/2012] [Indexed: 12/14/2022]
Abstract
Epidemiological studies have evaluated the association between IL-1β -511 C/T polymorphism and duodenal ulcer (DU) risk. However, the results remain conflicting. The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β -511 C/T polymorphism and DU. Systematic searches of electronic databases Embase, PubMed and Web of Science as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were performed. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 14 studies including 1887 cases and 2780 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β -511 C/T polymorphism and DU (for T allele vs. C allele: OR=0.93, 95% CI=0.82-1.06; for T/T vs. C/C: OR=0.83, 95% CI=0.64-1.08; for dominant model: OR=0.93, 95% CI=0.80-1.07; and for recessive model: OR=0.87, 95% CI=0.69-1.11). Significant association was found in all genetic models for the PB subgroup and sensitivity analyses. In conclusion, our meta-analysis suggests that there was no evidence of a significant association between IL-1β -511 C/T polymorphism and DU with or without Helicobacter pylori infection, whereas a significant association was found by sensitivity analyses which showed a protective effect of the T allele against DU risk.
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IL-1β (-511T/C) gene polymorphism not IL-1β (+3953T/C) and LT-α (+252A/G) gene variants confers susceptibility to visceral leishmaniasis. Mol Biol Rep 2012; 39:6907-14. [PMID: 22311026 DOI: 10.1007/s11033-012-1517-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2011] [Accepted: 01/24/2012] [Indexed: 01/11/2023]
Abstract
Lymphotoxin-α (LT-α) and interleukin-1beta (IL-1β) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-α (+252A/G) and IL-1β (+3953T/C and -511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was not found any significant differences in allele and genotype frequencies of LT-α (+252A/G) and IL-1β (+3953) among the study groups. However, the frequency of IL-1β -511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1β -511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1β CC (-511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1β -511C allele, CC genotype and CC (-511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1β -511TT genotype, T allele and TT haplotype (-511/+3953) might be counted as the influential factors for resistance to the disease.
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IL1B induced Smad 7 negatively regulates gastrin expression. PLoS One 2011; 6:e14775. [PMID: 21445336 PMCID: PMC3062540 DOI: 10.1371/journal.pone.0014775] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2010] [Accepted: 02/24/2011] [Indexed: 02/08/2023] Open
Abstract
Background Helicobacter pylori elicited IL1B is one of the various modulators responsible for perturbation of acid secretion in gut. We have earlier reported that IL1B activated NFkB downregulates gastrin, a major modulator of acid secretion. However, we hypothesized that regulation of gastrin by IL1B would depend on the cell's ability to integrate inputs from multiple signaling pathways to generate appropriate biological response. Principal Finding In this study, we report that IL1B induces Smad 7 expression by about 4.5 fold in gastric carcinoma cell line, AGS. Smad 7 resulted in transcriptional repression of gastrin promoter by about 6.5 fold when co -transfected with Smad 7 expression vector and gastrin-promoter luciferase in AGS cells. IL1B inhibited phosphorylation of Smad 3 and subsequently interfered with nuclear translocation of the positive Smad complex, thus occluding it off the gastrin promoter. IL1B promoter polymorphisms (-511T/-31C IL1B) are known to be associated with H. pylori associated gastro-duodenal ulcer. We observed that IL1B expressed from -31T promoter driven IL1B cDNA elicited 3.5 fold more Smad 7 than that expressed from the IL1B-31C variant in AGS cells. This differential activation of Smad 7 by IL1B promoter variants translated into differential downregulation of gastrin expression. We further analyzed Smad 7, NFkB, IL1B and gastrin expression in antral gut biopsy samples of patients with H. pylori associated duodenal ulcer and normal individuals. We observed that individuals with duodenal ulcer had significantly lower levels of IL1B, Smad 7, NFkB and corresponding higher level of gastrin expression. Conclusion Pro-inflammatory cytokine IL1B repress gastrin expression by activating Smad 7 and subsequent inhibition of nuclear localization of Smad 3/4 complex. Polymorphic promoter variants of IL1B gene can modulate the IL1B expression which resulted in differential activation Smad 7 and consequent repression of gastrin expression, respectively. Analysis of H. pylori infected duodenal ulcer patient's gut biopsy samples also supported this observation.
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Association of IL-1B genetic polymorphisms with an increased risk of opioid and alcohol dependence. Pharmacogenet Genomics 2010; 19:869-76. [PMID: 19801958 DOI: 10.1097/fpc.0b013e328331e68f] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE To examine the association between genetic variability of IL-1B, which encodes for the proinflammatory cytokine IL-1beta and the risk of developing opioid dependence. To confirm a previous study, we also examined the association between the IL-1B genetic polymorphism and alcohol dependence. METHODS Genomic DNA was isolated from 60 opioid-dependent, 99 alcohol-dependent patients and 60 healthy nondependent controls. Polymerase chain reaction and restriction fragment length polymorphism were used to determine the presence of single nucleotide polymorphisms at positions -511, -31 and 3954 of IL-1B. RESULTS IL-1B -511C and -31T alleles were more frequent in both the opioid-dependent and alcohol-dependent patients compared with the control group: odds ratio (OR, 95% confidence interval) P values corrected for false discovery rate=1.91 (1.14-3.20), P=0.043 and 1.89 (1.19-2.99), P=0.014, respectively, for IL-1B -511C>T; and OR=1.74 (1.02-2.97), P=0.066 and 1.80 (1.13-2.88), P=0.017, respectively, for IL-1B -31T>C. In contrast, no association was observed between opioid dependence and the IL-1B 3954C>T single nucleotide polymorphism [OR=1.60 (0.84-3.02), P=0.15]. CONCLUSION This study confirms the previous finding that IL-1B polymorphism is associated with altered risk of alcohol dependence. IL-1B single nucleotide polymorphisms at position -511 and -31, which increase IL-1beta production, occur at a higher frequency in opioid-dependent populations and may be associated, albeit weakly, with an increased risk of opioid dependence.
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Gawrońska-Szklarz B, Siuda A, Kurzawski M, Bielicki D, Marlicz W, Droździk M. Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole. Eur J Clin Pharmacol 2010; 66:681-7. [PMID: 20376628 DOI: 10.1007/s00228-010-0818-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2010] [Accepted: 03/21/2010] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Eradication of H. pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. Effects of PPI may depend on their metabolism, and other factors important for the pathophysiology of peptic ulcer disease. Aim of the present study was to evaluate an association of CYP2C19, MDR1, and IL-1B polymorphisms with the eradication rate of H. pylori in Polish Caucasian patients treated with a triple therapy of pantoprazole, amoxicillin, and metronidazole. METHODS A total of 139 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole + amoxicillin + metronidazole). Subsequently, the patients were divided into two groups (group 1, success, and group 2, failure of eradication after therapy) and genotyped by the PCR-RFLP method for the presence of CYP2C19 variant alleles (*2, *3, and *17), and MDR1 3435C>T and IL-1B +3954C>T polymorphisms. Pantoprazole serum concentrations were measured using the HPLC method. RESULTS No significant differences in frequency or distribution of CYP2C19 genotypes were found between the two groups of patients (i.e., with successful H. pylori eradication and treatment failure). However, any carrier of defective CYP2C19*2/*2 genotype was found among patients with treatment failure. Similarly, MDR1 and IL-1B genotypes were found to be significantly associated with the success or failure of H. pylori eradication. Univariate and multivariate analysis of the genotypes did not reveal any significant association between the genotypes and H. pylori eradication. Pantoprazole concentrations differed significantly, and were the highest in patients with defective allele CYP2C19*2 carriers and lowest in hyperactive genotype homozygotes CYP2C19*17/*17. CONCLUSION The results suggest that the CYP2C19 genotype contrary to MDR1 and IL-1B genotypes may have an impact on the efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole in Polish Caucasian peptic ulcer patients administered pantoprazole, amoxicillin, and metronidazole.
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Affiliation(s)
- Barbara Gawrońska-Szklarz
- Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland
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Gawrońska-Szklarz B, Siuda A, Kurzawski M, Bielicki D, Marlicz W, Droździk M. Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole. Eur J Clin Pharmacol 2010. [PMID: 20376628 DOI: 10.1007/s00228-010-0818-1.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Eradication of H. pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. Effects of PPI may depend on their metabolism, and other factors important for the pathophysiology of peptic ulcer disease. Aim of the present study was to evaluate an association of CYP2C19, MDR1, and IL-1B polymorphisms with the eradication rate of H. pylori in Polish Caucasian patients treated with a triple therapy of pantoprazole, amoxicillin, and metronidazole. METHODS A total of 139 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole + amoxicillin + metronidazole). Subsequently, the patients were divided into two groups (group 1, success, and group 2, failure of eradication after therapy) and genotyped by the PCR-RFLP method for the presence of CYP2C19 variant alleles (*2, *3, and *17), and MDR1 3435C>T and IL-1B +3954C>T polymorphisms. Pantoprazole serum concentrations were measured using the HPLC method. RESULTS No significant differences in frequency or distribution of CYP2C19 genotypes were found between the two groups of patients (i.e., with successful H. pylori eradication and treatment failure). However, any carrier of defective CYP2C19*2/*2 genotype was found among patients with treatment failure. Similarly, MDR1 and IL-1B genotypes were found to be significantly associated with the success or failure of H. pylori eradication. Univariate and multivariate analysis of the genotypes did not reveal any significant association between the genotypes and H. pylori eradication. Pantoprazole concentrations differed significantly, and were the highest in patients with defective allele CYP2C19*2 carriers and lowest in hyperactive genotype homozygotes CYP2C19*17/*17. CONCLUSION The results suggest that the CYP2C19 genotype contrary to MDR1 and IL-1B genotypes may have an impact on the efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole in Polish Caucasian peptic ulcer patients administered pantoprazole, amoxicillin, and metronidazole.
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Affiliation(s)
- Barbara Gawrońska-Szklarz
- Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland
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29
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Amirian E, Liu Y, Scheurer ME, El-Zein R, Gilbert MR, Bondy ML. Genetic variants in inflammation pathway genes and asthma in glioma susceptibility. Neuro Oncol 2010; 12:444-52. [PMID: 20406895 DOI: 10.1093/neuonc/nop057] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Single nucleotide polymorphisms (SNPs) in inflammation-related genes have previously been shown to alter risks of developing various cancers. However, the effects of such SNPs on glioma risk remain unclear. We used a multistrategic approach to elucidate the relationship between glioma risk, asthma/allergies, and 23 literature-based functional SNPs in 11 inflammation genes. Genotyping was conducted on 373 histologically confirmed adult glioma patients and 365 cancer-free controls from the Harris County Brain Tumor Study. Deviations from the Hardy-Weinberg equilibrium were assessed using the chi(2)-test, and Akaike's information criterion was used to determine the best genetic model for each SNP. Odds ratios (ORs) were calculated both for each SNP individually and for grouped analyses, examining the effects of the numbers of adverse alleles on glioma risk in participants with and without asthma. In the single-locus analysis of the 23 examined SNPs, 1 pro-inflammatory and 2 anti-inflammatory gene SNPs were significantly associated with glioma risk (COX2/PTGS2, rs20417 [OR = 1.41]; IL10, rs1800896 [OR = 1.57]; and IL13, rs20541 [OR = 0.39], respectively). When we examined the joint effects of the risk-conferring alleles of these 3 SNPs, we found a significant trend indicating that the risk increases as the number of adverse alleles increase (P = .005). Stratifying by asthma status, we found that this dose-response-like trend of increasing risk is only present among those without asthma/allergies (P < .0001). Our study indicates that polymorphisms in inflammation genes are associated with glioma susceptibility, especially when a history of asthma/allergies is absent.
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Affiliation(s)
- E Amirian
- Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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30
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Gehmert S, Velapatiño B, Herrera P, Balqui J, Santivañez L, Cok J, Vargas G, Combe J, Passaro DJ, Wen S, Meyer F, Berg DE, Gilman RH. Interleukin-1 beta single-nucleotide polymorphism's C allele is associated with elevated risk of gastric cancer in Helicobacter pylori-infected Peruvians. Am J Trop Med Hyg 2009; 81:804-10. [PMID: 19861615 DOI: 10.4269/ajtmh.2009.08-0494] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru.
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Affiliation(s)
- Sebastian Gehmert
- Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, 77054, USA.
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31
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Abstract
Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its incidence. Two important developments are associated with the decrease in rates of peptic ulcer disease: the discovery of effective and potent acid suppressants, and of Helicobacter pylori. With the discovery of H pylori infection, the causes, pathogenesis, and treatment of peptic ulcer disease have been rewritten. We focus on this revolution of understanding and management of peptic ulcer disease over the past 25 years. Despite substantial advances, this disease remains an important clinical problem, largely because of the increasingly widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. We discuss the role of these agents in the causes of ulcer disease and therapeutic and preventive strategies for drug-induced ulcers. The rare but increasingly problematic H pylori-negative NSAID-negative ulcer is also examined.
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Affiliation(s)
- Peter Malfertheiner
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
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32
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Misener VL, Gomez L, Wigg KG, King N, Kiss E, Daróczi G, Kapornai K, Tamás Z, Mayer L, Gádoros J, Baji I, Kennedy JL, Kovacs M, Vetró A, Barr CL. Tagging SNP association study of the IL-1beta gene (IL1B) and childhood-onset mood disorders. Am J Med Genet B Neuropsychiatr Genet 2009; 150B:653-9. [PMID: 19016479 DOI: 10.1002/ajmg.b.30885] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Given substantial evidence for IL-1beta involvement in the etiology of depression, the IL1B gene is a strong candidate for involvement in susceptibility to depressive disorders. However, association studies investigating this, to date, have been limited to just two polymorphisms (rs1143627[-31T/C] and rs16944[-511C/T]) that constitute only a fraction of the genetic variation that is actually present across this gene in the population. Here, in a family-based association study of childhood-onset mood disorders (COMD), characterized by onset of depression before the age of 15, we have used a gene-wide approach, employing a panel of five tagging SNPs spanning the entire gene. Based on TDT analyses of both individual alleles and haplotypes, in a study sample of 646 families (with 782 affected children), none of the SNPs, including those implicated in transcriptional regulation of the gene, showed evidence for association with COMD. This is the largest and most comprehensive study of IL1B in relation to mood disorders that has been carried out, to date. The results do not support the involvement of IL1B as a major factor in genetic risk for early-onset mood disorders.
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Affiliation(s)
- Virginia L Misener
- Toronto Western Research Institute, University Health Network, Ontario, Canada
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33
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Suzuki K, Inoue T, Yanagisawa A, Kimura A, Ito Y, Hamajima N. Association between Interleukin-1B C-31T polymorphism and obesity in Japanese. J Epidemiol 2009; 19:131-5. [PMID: 19398847 PMCID: PMC3924137 DOI: 10.2188/jea.je20081015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background Recent studies have revealed a close relationship between obesity and polymorphism in the inflammation gene. However, the association between interleukin-1beta (IL-1β) and obesity remains controversial. We therefore investigated the association between IL-1B C-31T polymorphism and obesity in Japanese. Methods The participants were 802 inhabitants (281 men and 521 women) of Japan, aged 39 to 88 years, who attended a health examination in 2003. Body height, weight, waist and hip circumferences, and body fat percentage were measured. The IL-1B C-31T polymorphism was genotyped by polymerase chain reaction with confronting 2-pair primers. The association between IL-1B C-31T genotypes and various indices of obesity was then investigated. The confounding factor-adjusted odds ratios (OR) and 95% confidence intervals (CI) for obesity were calculated for each IL-1B C-31T genotype by using unconditional logistic regression analysis. Results Among male carriers of the CT and TT genotypes, the ORs for high body fat percentage were 2.58 (95% CI, 1.17–6.34) and 2.81 (1.17–7.33), respectively, as compared to carriers of the CC genotype (P for trend = 0.037). Among women, carriers of the TT genotype had significantly higher ORs for high BMI (OR, 2.13; 95% CI, 1.25–3.67) and large waist circumference (2.49; 1.37–4.66), as compared to women with the CC genotype (P for trend = 0.005 and 0.004, respectively). Conclusions The IL-1B C-31T polymorphism is associated with obesity in Japanese. Men and women with the TT genotype of IL-1B C-31T had a higher risk for obesity than those with the CC genotype.
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Affiliation(s)
- Koji Suzuki
- Department of Public Health, School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan.
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Chakravorty M, Datta De D, Choudhury A, Santra A, Roychoudhury S. Association of specific haplotype of TNFalpha with Helicobacter pylori-mediated duodenal ulcer in eastern Indian population. J Genet 2009; 87:299-304. [PMID: 19147919 DOI: 10.1007/s12041-008-0048-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Meenakshi Chakravorty
- Molecular and Human Genetics, Indian Institute of Chemical Biology, Kolkata 700 032, India
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35
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Chakravorty M, Datta De D, Choudhury A, Roychoudhury S. IL1B promoter polymorphism regulates the expression of gastric acid stimulating hormone gastrin. Int J Biochem Cell Biol 2009; 41:1502-10. [PMID: 19166966 DOI: 10.1016/j.biocel.2008.12.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2008] [Revised: 12/17/2008] [Accepted: 12/22/2008] [Indexed: 12/16/2022]
Abstract
It is important to dissect the effect of the alternative alleles of a functional SNP on the entire biochemical pathway for the complete understanding of the mechanism of the manifestation of complex diseases. IL1B-511C>T and -31C>T promoter polymorphisms have been suggested as potential susceptibility loci for Helicobacter pylori associated gastroduodenal diseases. We report that altered expression of IL1B due to a specific polymorphism in its promoter modulates the expression of gastrin, an acid regulating hormone. Treatment of gastric carcinoma cells, AGS, with IL1B resulted in a 20-fold reduction in gastrin expression. Gastrin promoter assay showed that IL1B inhibits gastrin expression at the transcriptional level and part of this inhibitory process is mediated via activation of NFkappaB and involvement of HDACs. An almost 3-fold increase in IL1B expression was observed when AGS cells were transfected with -31TIL1B expression plasmid in comparison to -31CIL1B. The -31TIL1B induced a 2-fold greater repression of the gastrin luciferase activity compared to -31CIL1B. This signaling of the -31TIL1B variant allele driven IL1B revealed an almost 1.5-fold greater expression of NFkappaB. Thus, this study showed that a single base substitution at the -31 position of the IL1B promoter brought about differential expression of IL1B which differentially altered both NFkappaB activation and gastrin expression.
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Affiliation(s)
- Meenakshi Chakravorty
- Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Raja S.C. Mullick Road, Kolkata, India
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36
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Lee JM, Kang YR, Park SH, Cha SI, Kim JS, Kang HK, Lee WK, Kim MJ, Kim CH, Kim NS, Jung TH, Park JY. Polymorphisms in interleukin-1B and its receptor antagonist genes and the risk of chronic obstructive pulmonary disease in a Korean population: a case–control study. Respir Med 2008; 102:1311-20. [DOI: 10.1016/j.rmed.2008.03.026] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2007] [Revised: 03/06/2008] [Accepted: 03/25/2008] [Indexed: 11/30/2022]
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Abstract
PURPOSE OF REVIEW To examine the type and risk of infections in humans and mice deficient in proinflammatory cytokines. Naturally occurring or manipulated genetic defects of tumor necrosis factor, interleukins-1, -6, -12, and -15, and interferon-gamma are examined for their increased susceptibility to, or protection from, infection. RECENT FINDINGS Interleukin-12p40 and interferon-gamma-blockers may lead to increased incidence of infections with intracellular bacteria, parasites, and fungi. In addition, we may see viral infections with interferon-gamma-blockers. Increased risk of infections is unlikely with either interleukin-1- or interleukin-15-blockers. Interleukin-6-blockers may lead to increased risk of infection with extracellular bacteria, viruses, parasites and fungi. SUMMARY In tumor necrosis factor knockout mice, increased susceptibility to pathogens are reported that are normally controlled by granuloma formation. In patients treated with tumor necrosis factor-blockers, a two-fold increase of granulomatous infections, predominantly reactivation of latent tuberculosis, is found. The infections detected in tumor necrosis factor knockout mice were accurate for predicting the infections observed when using tumor necrosis factor-blockers. If a similar correlation exists for other cytokines, the use of interferon-gamma and interleukin-12p40 blockers, and possibly interleukin-6 blockers, will lead to an increased risk for severe infections. Care should be taken when new cytokine blockers/antagonists are introduced.
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Lind H, Haugen A, Zienolddiny S. Differential binding of proteins to the IL1B -31 T/C polymorphism in lung epithelial cells. Cytokine 2007; 38:43-8. [PMID: 17587593 DOI: 10.1016/j.cyto.2007.05.001] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2007] [Revised: 03/16/2007] [Accepted: 05/03/2007] [Indexed: 12/20/2022]
Abstract
Chronic inflammation has been implicated as a cofactor in the development of several human cancers. Interleukin-1beta is a key pro-inflammatory cytokine. We have previously shown associations between polymorphisms at position -511 and -31 in the promoter of the IL1B gene and risk of non-small cell lung cancer. In this study we investigated the functional role of the -31 T/C SNP in the regulation of the IL1B gene. The -31 T/C polymorphism is located in the core promoter and may affect the binding of transcription factors and thereby promoter activity. We therefore established a promoter reporter assay to explore the impact of the promoter variants on the expression of the gene. In the present study, we show that expression from the T-variant of the promoter was higher (p<0.001) than from the C-variant, in A549 cells. Electrophoretic mobility shift assays revealed differential binding of proteins to a promoter fragment containing the SNP. Interestingly, a highly specific complex formed on the C-variant that was not present on the T-variant. Supershift experiments implicated binding of both the CCAAT-enhancer binding protein beta (C/EBPbeta, also called NF-IL6) transcription factor and the TATA-box binding protein (TBP) to the SNP region. Due to the high frequency of this SNP, differences in IL1B gene expression caused by the variants may have significant biological impact in the population.
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Affiliation(s)
- Helge Lind
- Section for Toxicology, Department of Chemical and Biological Working Environment, National Institute of Occupational Health, Oslo, Norway
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39
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Singh RK, Indra D, Mitra S, Mondal RK, Basu PS, Roy A, Roychowdhury S, Panda CK. Deletions in chromosome 4 differentially associated with the development of cervical cancer: evidence of slit2 as a candidate tumor suppressor gene. Hum Genet 2007; 122:71-81. [PMID: 17609981 DOI: 10.1007/s00439-007-0375-6] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2007] [Accepted: 04/30/2007] [Indexed: 01/11/2023]
Abstract
The aim of this study was to locate the candidate tumor suppressor genes (TSGs) loci in the chromosomal 4p15-16, 4q22-23 and 4q34-35 regions associated with the development of uterine cervical carcinoma (CA-CX). Deletion mapping of the regions by microsatellite markers identified six discrete areas with high frequency of deletions, viz. 4p16.2 (D1: 40%), 4p15.31 (D2: 35-38%), 4p15.2 (D3: 37-40%), 4q22.2 (D4: 34%), 4q34.2-34.3 (D5: 37-59%) and 4q35.1 (D6: 40-50%). Significant correlation was noted among the deleted regions D1, D2 and D3. The deletions in D1, D2, D5 and D6 regions are suggested to be associated with the cervical intraepithelial neoplasia (CIN), and deletions in the D2, D3, D5 and D6 regions seems to be associated with progression of CA-CX. The deletions in the D2 and D6 regions showed significant prognostic implications (P = 0.001; 0.02). The expression of the candidate TSG SLIT2 mapped to D2 region gradually reduced from normal cervix uteri -->CIN --> CA-CX. SLIT2 promoter hypermethylation was seen in 28% CIN samples and significantly increased with tumor progression (P = 0.04). Significant correlation was seen between SLIT2 deletion and its promoter methylation (P = 0.001), indicating that both these phenomena could occur simultaneously to inactivate this gene. Immunohistochemical analysis showed reduced expression of SLIT2 in cervical lesions and CA-CX cell lines. Although no mutation was detected in the SLIT2 promoter region (-432 to + 55 bp), CC and AA haplotypes were seen in -227 and -195 positions, respectively. Thus, it indicates that inactivation of SLIT2-ROBO1 signaling pathway may have an important role in CA-CX development.
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MESH Headings
- Adult
- Aged
- Carcinoma, Squamous Cell/complications
- Carcinoma, Squamous Cell/genetics
- Carcinoma, Squamous Cell/metabolism
- Carcinoma, Squamous Cell/mortality
- Chromosome Deletion
- Chromosomes, Human, Pair 4
- DNA Methylation
- DNA Mutational Analysis
- Female
- Gene Expression Regulation, Neoplastic
- Genes, Tumor Suppressor
- Genetic Predisposition to Disease
- HeLa Cells
- Humans
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/metabolism
- Middle Aged
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism
- Papillomavirus Infections/complications
- Papillomavirus Infections/epidemiology
- Promoter Regions, Genetic
- RNA, Messenger/metabolism
- Survival Analysis
- Tumor Cells, Cultured
- Uterine Cervical Neoplasms/complications
- Uterine Cervical Neoplasms/genetics
- Uterine Cervical Neoplasms/metabolism
- Uterine Cervical Neoplasms/mortality
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Affiliation(s)
- Ratnesh Kumar Singh
- Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India
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40
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Akhter Y, Ahmed I, Devi SM, Ahmed N. The co-evolved Helicobacter pylori and gastric cancer: trinity of bacterial virulence, host susceptibility and lifestyle. Infect Agent Cancer 2007; 2:2. [PMID: 17201930 PMCID: PMC1769358 DOI: 10.1186/1750-9378-2-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2006] [Accepted: 01/04/2007] [Indexed: 12/29/2022] Open
Abstract
Helicobacter pylori is an important yet unproven etiological agent of gastric cancer. H. pylori infection is more prevalent in developing Asian countries like India and it is usually acquired at an early age. It has been two decades since Marshall and Warren (1984) first described curved bacilli in the stomach of ulcer and gastritis patients. This discovery has won them the Nobel Prize recently, but the debate whether H. pylori is a pathogen or a commensal organism is still hot. Associations with disease-specific factors remain illusive years after the genome sequences were made available. Cytotoxin-associated antigen A (CagA) and the so-called plasticity region cluster genes are implicated in pathogenesis of the carcinoma of stomach. Another virulence factor VacA whose role is still debatable, has recently been projected in pathology of gastric cancer. Studies of the evolution through genetic variation in H. pylori populations have provided a window into the history of human population migrations and a possible co-evolution of this pathogen with its human host. Possible symbiotic relationships were seriously debated since the discovery of this pathogen. The debate has been further intensified as some studies proposed H. pylori infection to be beneficial in some humans. In this commentary, we attempt to briefly discuss about H. pylori as a human pathogen, and some of the important issues linked to its pathophysiology in different hosts. 'We dance around in a ring and suppose, the secret sits in the middle and knows' – Robert Frost
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Affiliation(s)
- Yusuf Akhter
- Pathogen Evolution Group, Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India
| | - Irshad Ahmed
- Department of Microbiology, Shri Shivaji College of Arts, Commerce and Science, Akola, India
| | - S Manjulata Devi
- Pathogen Evolution Group, Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India
| | - Niyaz Ahmed
- Pathogen Evolution Group, Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India
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Abstract
The prevalence of Helicobacter pylori-associated peptic ulcers, in particular duodenal ulcers, is decreasing following decreasing prevalence of H. pylori infection, while the frequency of non-steroidal anti-inflammatory drugs (NSAIDs)-induced and H. pylori-negative idiopathic ulcers is increasing. The incidence of bleeding ulcers has been stable during the last decades. Several putative H. pylori virulence genes, i.e., cag, vacA, babA, or dupA, as well as host-related genetic factors like IL-1beta and TNFalpha-gene polymorphism, have been proposed as risk factors for duodenal ulcer. H. pylori eradication may prevent NSAID complications, in particular, when it is performed before introduction of NSAIDs. There is a complex association between H. pylori and gastroesophageal reflux disease (GERD), and the impact of H. pylori eradication on the appearance of GERD symptoms depends on various host- and bacteria-related factors. Eradication of H. pylori in GERD is recommended in patients before instauration of a long-term PPI treatment to prevent the development of gastric atrophy. A small proportion (10%) of non-ulcer dyspepsia cases may be attributed to H. pylori and may benefit from eradication treatment. A test-and-treat strategy is more cost-effective than prompt endoscopy in the initial management of dyspepsia.
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