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Park SY, Bae H, Jeong HY, Lee JY, Kwon YK, Kim CE. Identifying Novel Subtypes of Functional Gastrointestinal Disorder by Analyzing Nonlinear Structure in Integrative Biopsychosocial Questionnaire Data. J Clin Med 2024; 13:2821. [PMID: 38792363 PMCID: PMC11122158 DOI: 10.3390/jcm13102821] [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: 03/26/2024] [Revised: 04/26/2024] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
Background/Objectives: Given the limited success in treating functional gastrointestinal disorders (FGIDs) through conventional methods, there is a pressing need for tailored treatments that account for the heterogeneity and biopsychosocial factors associated with FGIDs. Here, we considered the potential of novel subtypes of FGIDs based on biopsychosocial information. Methods: We collected data from 198 FGID patients utilizing an integrative approach that included the traditional Korean medicine diagnosis questionnaire for digestive symptoms (KM), as well as the 36-item Short Form Health Survey (SF-36), alongside the conventional Rome-criteria-based Korean Bowel Disease Questionnaire (K-BDQ). Multivariate analyses were conducted to assess whether KM or SF-36 provided additional information beyond the K-BDQ and its statistical relevance to symptom severity. Questions related to symptom severity were selected using an extremely randomized trees (ERT) regressor to develop an integrative questionnaire. For the identification of novel subtypes, Uniform Manifold Approximation and Projection and spectral clustering were used for nonlinear dimensionality reduction and clustering, respectively. The validity of the clusters was assessed using certain metrics, such as trustworthiness, silhouette coefficient, and accordance rate. An ERT classifier was employed to further validate the clustered result. Results: The multivariate analyses revealed that SF-36 and KM supplemented the psychosocial aspects lacking in K-BDQ. Through the application of nonlinear clustering using the integrative questionnaire data, four subtypes of FGID were identified: mild, severe, mind-symptom predominance, and body-symptom predominance. Conclusions: The identification of these subtypes offers a framework for personalized treatment strategies, thus potentially enhancing therapeutic outcomes by tailoring interventions to the unique biopsychosocial profiles of FGID patients.
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Affiliation(s)
- Sa-Yoon Park
- Department of Physiology, College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (S.-Y.P.); (H.-Y.J.)
- Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea
| | - Hyojin Bae
- Department of Physiology, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea;
| | - Ha-Yeong Jeong
- Department of Physiology, College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (S.-Y.P.); (H.-Y.J.)
| | - Ju Yup Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea;
| | - Young-Kyu Kwon
- Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Chang-Eop Kim
- Department of Physiology, College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (S.-Y.P.); (H.-Y.J.)
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Li RJ, Xu JY, Wang X, Liao LJ, Wei X, Xie P, Xu WY, Xu ZY, Xie SH, Jiang YY, Huang L, Wang LY, Huang GR, Huang YQ. Therapeutic effect of demethylated hydroxylated phillygenin derivative on Helicobacter pylori infection. Front Microbiol 2023; 14:1071603. [PMID: 37275170 PMCID: PMC10235509 DOI: 10.3389/fmicb.2023.1071603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 05/04/2023] [Indexed: 06/07/2023] Open
Abstract
Modifying and transforming natural antibacterial products is a novel idea for developing new efficacious compounds. Phillygenin has an inhibitory effect on H. pylori. The aim of the present study was to prepare a phillygenin derivative (PHI-Der) through demethylation and hydroxylation. The minimum inhibitory concentration of 18 strains of H. pylori from different sources was 8-32 μg/mL in vitro, and the activity increased 2-8 times than that of phillygenin. PHI-Der could significantly inhibit the colonization of H. pylori in vivo, reduce the inflammatory response, and promote the repair of inflammatory damage. Further, we used SwissTargetPrediction to predict that its main targets are ALOX5, MCL1, and SLC6A4, and find that it can inhibit bacterial biofilm formation and reduce bacterial infection of cells. It can enhance the intracellular oxidative capacity of H. pylori to inhibit H. pylori growth. Further, it could prevent the oxidation of H. pylori-infected cells and reduce the inflammatory response, which plays a role in protection. In conclusion, compared to phillygenin, PHI-Der had better antibacterial activity and was more effective in treating H. pylori infection. It has characteristics of high safety, specificity, resistance to drug resistance and better antibacterial activity than phillygenin, it's a good antioxidant for host cells.
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Affiliation(s)
- Ru-Jia Li
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
- Clinical Laboratory of 980 Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, Hebei, China
| | - Jia-yin Xu
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Xue Wang
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Li-juan Liao
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Xian Wei
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Ping Xie
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Wen-yan Xu
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Zhen-yi Xu
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Shuo-hua Xie
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Yu-ying Jiang
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Liang Huang
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Lu-yao Wang
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Gan-rong Huang
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
| | - Yan-Qiang Huang
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, China
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Wang Z, Wu L, Dong P, Wang Q, Sun X, Liu L, Guo Y, Sun Y, Shu T. Meta-Analysis of the Association Between 5-Hydroxytryptamine Transporter Gene-Linked Polymorphic Region and Functional Dyspepsia and its Subtypes. Genet Test Mol Biomarkers 2023; 27:100-108. [PMID: 36989523 DOI: 10.1089/gtmb.2022.0151] [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: 03/31/2023] Open
Abstract
Background: Association studies of variations in the 5-hydroxytryptamine (5-HT, serotonin) transporter gene-linked polymorphic region (5-HTTLPR) and functional dyspepsia (FD) have yielded contradictory results. Hence, we performed a meta-analysis to clarify inconsistencies between the 5-HTTLPR polymorphism with FD and it subtypes. Methods: We performed a literature search in PubMed, Embase, Web of Science, Cochrane Library, and CNKI, including articles published until March 2022. We calculated and pooled odds ratios (ORs) with their 95% confidence intervals (CIs) in Stata 15.0. Data extraction was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane Handbook for Systematic Reviews of Interventions. Results: The meta-analysis included six studies, comprising 488 cases and 1513 healthy controls. We did not observe a significant association between the 5-HTTLPR polymorphism and FD in the overall population. In subgroup analyses, the 5-HTTLPR polymorphism was significantly associated with FD-subtype epigastric pain syndrome (EPS) (SS vs. LL+LS, OR = 0.620, 95% CI: 0.414-0.930; SS vs. LS, OR = 0.640, 95% CI: 0.417-0.980; S vs. L, OR = 0.655, 95% CI: 0.471-0.911). However, no association was observed with the other subtype, postprandial distress syndrome (PDS). Conclusion: While the 5-HTTLPR polymorphism had no relationship with FD overall, splitting the disease into its subtypes revealed a clear association with EPS.
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Affiliation(s)
- Zhiming Wang
- School of Medicine, Southwest Jiaotong University, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
| | - Liping Wu
- School of Medicine, Southwest Jiaotong University, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
- Department of Gastroenterology, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
| | - Peiwen Dong
- Department of Gastroenterology, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
| | - Qiong Wang
- Department of Gastroenterology, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
| | - Xiaobin Sun
- School of Medicine, Southwest Jiaotong University, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
- Department of Gastroenterology, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
| | - Lei Liu
- Medical Research Center, the Third People's Hospital of Chengdu, the Affiliated Hospital of Southwest Jiaotong University, the Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan, China
| | - Yuanbiao Guo
- Medical Research Center, the Third People's Hospital of Chengdu, the Affiliated Hospital of Southwest Jiaotong University, the Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan, China
| | - Yueshan Sun
- Medical Research Center, the Third People's Hospital of Chengdu, the Affiliated Hospital of Southwest Jiaotong University, the Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan, China
| | - Tao Shu
- Department of Gastroenterology, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu, China
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Lee JY, Kim N, Park JH, Yu JE, Song YJ, Yoon JW, Lee DH. Sex and Gender Differences in Overlap Syndrome of Functional Gastrointestinal Disorder and Effect of Genetic Polymorphisms in South Korea: A Long-term Follow-up Study. J Neurogastroenterol Motil 2022; 28:145-158. [PMID: 34980697 PMCID: PMC8748849 DOI: 10.5056/jnm21047;] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 10/02/2021] [Accepted: 10/11/2021] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND/AIMS Overlap functional gastrointestinal disorder (FGID) is associated with more severe gastrointestinal symptoms and lower quality of life. The aim of this study is to evaluate clinical features of non-erosive reflux disease (NERD), functional dyspepsia, irritable bowel syndrome, their overlap in terms of sex and gender, and to assess the risk factors, including genetic polymorphisms. METHODS A total of 494 FGIDs and 239 controls were prospectively enrolled between 2004 and 2020. FGIDs were diagnosed based on the Rome III criteria and symptoms were evaluated using a questionnaire. Follow-up questionnaires were conducted to determine the change of symptoms during the 75.8-month mean observation period. Risk factors including genetic polymorphisms in neurotransmitter receptor (SLC6A4 5-HTTLPR, GNB3, ADRA2A, CCKAR, and TRPV1) and cytokine (TNFA and IL10) genes. RESULTS NERD was more prevalent in men, and functional dyspepsia in women. Overlap FGIDs (n = 239) were more prevalent than nonoverlap FGIDs (n = 255) in women (P = 0.019). Anxiety and depression scores were higher in the overlaps (P = 0.012 and P < 0.001, respectively). Symptoms were more frequent and severe in the overlap FGIDs than in the non-overlaps (P < 0.001). During followup, symptoms progressed more frequently in the overlap FGIDs, especially in patients with the L/S genotype of SLC6A4 5-HTTLPR and anxiety/depression. CONCLUSIONS Overlap FGID patients need attention given their association with anxiety/depression and more severe symptoms, especially in women. Genetic polymorphisms also may be associated with certain symptoms of overlap FGIDs.
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Affiliation(s)
- Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Eun Yu
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Yun Jeong Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Jung Won Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Lee JY, Kim N, Park JH, Yu JE, Song YJ, Yoon JW, Lee DH. Sex and Gender Differences in Overlap Syndrome of Functional Gastrointestinal Disorder and Effect of Genetic Polymorphisms in South Korea: A Long-term Follow-up Study. J Neurogastroenterol Motil 2022; 28:145-158. [PMID: 34980697 PMCID: PMC8748849 DOI: 10.5056/jnm21047] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 10/02/2021] [Accepted: 10/11/2021] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Overlap functional gastrointestinal disorder (FGID) is associated with more severe gastrointestinal symptoms and lower quality of life. The aim of this study is to evaluate clinical features of non-erosive reflux disease (NERD), functional dyspepsia, irritable bowel syndrome, their overlap in terms of sex and gender, and to assess the risk factors, including genetic polymorphisms. Methods A total of 494 FGIDs and 239 controls were prospectively enrolled between 2004 and 2020. FGIDs were diagnosed based on the Rome III criteria and symptoms were evaluated using a questionnaire. Follow-up questionnaires were conducted to determine the change of symptoms during the 75.8-month mean observation period. Risk factors including genetic polymorphisms in neurotransmitter receptor (SLC6A4 5-HTTLPR, GNB3, ADRA2A, CCKAR, and TRPV1) and cytokine (TNFA and IL10) genes. Results NERD was more prevalent in men, and functional dyspepsia in women. Overlap FGIDs (n = 239) were more prevalent than non-overlap FGIDs (n = 255) in women (P = 0.019). Anxiety and depression scores were higher in the overlaps (P = 0.012 and P < 0.001, respectively). Symptoms were more frequent and severe in the overlap FGIDs than in the non-overlaps (P < 0.001). During follow-up, symptoms progressed more frequently in the overlap FGIDs, especially in patients with the L/S genotype of SLC6A4 5-HTTLPR and anxiety/depression. Conclusions Overlap FGID patients need attention given their association with anxiety/depression and more severe symptoms, especially in women. Genetic polymorphisms also may be associated with certain symptoms of overlap FGIDs.
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Affiliation(s)
- Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Eun Yu
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Yun Jeong Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Jung Won Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Nam K, Kim N, Song HJ, Baik GH, Choi SC, Kim HJ, Lee JY, Park KS, Park SY, Park SJ. Gender difference in the overlap of irritable bowel syndrome and functional dyspepsia: a prospective nationwide multicenter study in Korea. J Gastroenterol 2021; 56:537-546. [PMID: 33687537 DOI: 10.1007/s00535-021-01775-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 02/27/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND The overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS) is associated with more severe gastrointestinal (GI) symptoms and lower quality of life. However, the gender differences in FD-IBS overlap remain unclear. This study aimed to investigate the gender differences in patients with FD-IBS overlap. METHODS Controls and cases were prospectively enrolled from July 2019 to June 2020 at nine tertiary referral centers. The patients underwent esophagogastroduodenoscopy, and their symptoms were evaluated using a questionnaire including GI symptom-related items and the Hospital Anxiety Depression Scale (HADS). FD and IBS were diagnosed according to the Rome IV criteria, and the clinical characteristics of the FD-IBS overlap group were compared with those of the FD-only or IBS-only group. RESULTS Among 667 subjects (334 healthy controls, 168 with FD-only, 37 with IBS-only, 128 with FD-IBS overlap), the FD-IBS overlap group (19.2%) showed a higher rate of preference for dairy products, a higher rate of history of Helicobacter pylori eradication, and higher HADS scores than the non-overlap group (P < 0.05). In the FD-IBS overlap group, men complained of reflux symptom and loose/watery stools more than women (P < 0.05), whereas women showed more severe GI symptoms, especially epigastric pain/burning symptoms, and higher depression scores than men (all P < 0.05). CONCLUSIONS FD-IBS overlap patients are associated with severe upper GI symptoms and depression compared to non-overlap patients. Moreover, women with FD-IBS overlap experience more severe GI and depression symptoms than men.
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Affiliation(s)
- Kwangwoo Nam
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Korea.
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
| | - Hyun Joo Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Suck Chei Choi
- Department of Internal Medicine, Digestive Disease Research Institute, Wonkwang University College of Medicine, Iksan, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Ju Yup Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sun-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Seun Ja Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
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Yuan C, Yong G, Wang X, Xie T, Wang C, Yuan Y, He G. Developing the Patient Health Questionnaire-8 for a greater impact on the quality of life of patients with functional dyspepsia compared to Somatic Symptom Scale-8. BMC Gastroenterol 2020; 20:359. [PMID: 33115439 PMCID: PMC7594451 DOI: 10.1186/s12876-020-01508-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 10/19/2020] [Indexed: 02/08/2023] Open
Abstract
Background To develop the Patient Health Questionnaire-8 (PHQ-8) as a more reliable approach than the Somatic Symptom Scale-8 (SSS-8), evaluating somatization which might be a critical factor influencing the quality of life (QoL) in patients with functional dyspepsia (FD). Also, the effects of somatization on QoL of FD patients were assessed by these two approaches. Methods Herein, 612 FD patients completed a questionnaire involving 25 items. 8/25 items were selected to develop the PHQ-8 by four methods of discrete degree, correlation coefficient, factor analysis, and Cronbach’s α coefficient. Reliability and validity of the PHQ-8 and the SSS-8 were compared by principal component and confirmatory factor analyses. The effects of somatization, depression, and anxiety on the Nepean Dyspepsia Index (NDI) for QoL were explored by Pearson’s correlation coefficient and linear regression analysis. Results The Cronbach’s α coefficient for the PHQ-8 and the SSS-8 was 0.601 and 0.553, respectively, and the cumulative contribution rate of three extracted factors for the developed PHQ-8 and SSS-8 was 55.103% and 51.666%, respectively. Somatization evaluated by the PHQ-8 (r = 0.309, P < 0.001) and the SSS-8 (r = 0.281, P < 0.001) was found to be correlated to NDI. The model used for the PHQ-8 showed that the values of goodness-of-fit index (GFI) and adjusted GFI (AGFI) were 0.984 and 0.967, respectively, which indicated that the model fitted well. Linear regression analysis unveiled that somatization (β = 0.270, P < 0.001), anxiety (β = 0.163, P < 0.001), and depression (β = 0.136, P = 0.003) assessed by the PHQ-8 were correlated to NDI. In addition, somatization (β = 0.250, P < 0.001), anxiety (β = 0.156, P < 0.001), and depression (β = 0.155, P = 0.001) evaluated by the SSS-8 were correlated to NDI. Conclusions PHQ-8 showed a superior reliability and validity, and somatization assessed by the developed PHQ-8 showed a greater influence on the QoL of FD patients as compared to the SSS-8. Our findings suggested that the developed PHQ-8 may show improvement in a reliable assessment of the effects of somatization on FD patients in lieu of the SSS-8.
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Gene Polymorphisms and Susceptibility to Functional Dyspepsia: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019:3420548. [PMID: 31178907 PMCID: PMC6501140 DOI: 10.1155/2019/3420548] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 01/15/2019] [Accepted: 02/03/2019] [Indexed: 12/16/2022] Open
Abstract
Functional dyspepsia (FD) is a common chronic gastrointestinal disorder with a complex, undefined mechanism. Clustering of patients with FD in families highlights the role of genetic factors in the pathogenesis of FD. We performed a systematic review and meta-analysis to clarify the associations between specific gene polymorphisms and FD susceptibility. PubMed, EMBASE, the Cochrane Library, and HuGE database were searched. An additive model was adopted to determine whether previous studied genes are associated with FD susceptibility. Carriers of minor allele in GNB3 825C>T (OR = 1.15, 95% CI 0.99-1.34, P = 0.07), SCL6A4 5HTTLPR (OR = 0.92, 95% CI 0.75-1.12, P = 0.40), and CCK-1R 779T>C (OR = 0.86, 95% CI 0.72-1.03, P = 0.09) genes failed to demonstrate susceptibility to FD. In a subgroup analysis, only minor allele (T) in GNB3 825C>T was associated with an increased susceptibility to the epigastric pain syndrome subtype (OR = 1.34, 95% CI 1.10-1.63, P = 0.003). Our meta-analysis based on available studies using an additive model failed to show that GNB3, SCL6A4, and CCK-1R polymorphisms are associated with FD susceptibility.
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Tanaka F, Tominaga K, Fujikawa Y, Morisaki T, Otani K, Hosomi S, Nagami Y, Kamata N, Taira K, Nakano A, Kimura T, Yamagami H, Tanigawa T, Morikawa H, Fukumoto S, Watanabe T, Kawada N, Hirata K, Fujiwara Y. Association between Functional Dyspepsia and Gastric Depressive Erosions in Japanese Subjects. Intern Med 2019; 58:321-328. [PMID: 30210122 PMCID: PMC6395123 DOI: 10.2169/internalmedicine.1325-18] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective The association between functional dyspepsia (FD) and endoscopic findings has not been fully elucidated. Helicobacter pylori infection is considered a key factor in the pathophysiology of FD. The Kyoto Classification of Gastritis (KCG) was proposed in 2014 to evaluate endoscopic findings based on the H. pylori status. We investigated the endoscopic findings associated with FD according to the KCG. Methods This cross-sectional study included subjects who underwent esophagogastroduodenoscopy during a medical health check-up. We compared the endoscopic findings between subjects with FD and healthy controls (HCs) according to the KCG. Results A total of 456 subjects were analyzed. Among them, the detection rate of FD was 5.5% (25/456 persons). In a univariate analysis of the endoscopic findings, a significantly lower proportion of subjects with FD had gastric red streak in comparison to HCs (0% vs. 18.6%, respectively; p=0.0124). Subjects with FD were more likely to have gastric depressive erosion (20.0% vs. 7.9%; p=0.0522). A higher proportion of the erosion-positive subjects had FD in comparison to erosion-negative subjects (12.8% vs. 4.8%). There were no significant differences in the other endoscopic findings, including gastric atrophy, intestinal metaplasia, enlarged fold, nodularity, and diffuse redness. A multivariate analysis revealed that gastric depressive erosion was significantly and independently associated with FD (odds ratio, 2.92; 95% confidence interval, 1.03-8.26; p=0.0436). In contrast, gastric red streak was not associated with FD (p=0.989). Conclusion Gastric depressive erosions may be associated with dyspepsia.
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Affiliation(s)
- Fumio Tanaka
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Kazunari Tominaga
- Premier Developmental Research of Medicine, Osaka Medical College, Japan
| | - Yoshiko Fujikawa
- Premier Developmental Research of Medicine, Osaka Medical College, Japan
| | - Tamami Morisaki
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Koji Otani
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Shuhei Hosomi
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Yasuaki Nagami
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Noriko Kamata
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Koichi Taira
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Akemi Nakano
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Tatsuo Kimura
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Hirokazu Yamagami
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Tetsuya Tanigawa
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Hiroyasu Morikawa
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Shinya Fukumoto
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Toshio Watanabe
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Norifumi Kawada
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Kazuto Hirata
- Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Japan
| | - Yasuhiro Fujiwara
- Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
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Choi YJ, Park YS, Kim N, Kim YS, Lee SM, Lee DH, Jung HC. Gender differences in ghrelin, nociception genes, psychological factors and quality of life in functional dyspepsia. World J Gastroenterol 2017; 23:8053-8061. [PMID: 29259381 PMCID: PMC5725300 DOI: 10.3748/wjg.v23.i45.8053] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 09/27/2017] [Accepted: 11/07/2017] [Indexed: 02/06/2023] Open
Abstract
AIM to evaluate gender differences in the aspect of ghrelin, nociception-related genes and psychological aspects and the quality of life (QoL) in Korean functional dyspepsia (FD) patients.
METHODS Total of 191 persons were prospectively enrolled between March 2013 and May 2016 in Seoul National Bundang Hospital, and classified into control and FD group based on ROME III criteria. Questionnaire included assessment for dyspepsia symptoms, QoL and anxiety or depression. Preproghrelin and nociception genes in the gastric mucosa and plasma acyl/des-acyl ghrelin were measured.
RESULTS Lower level of plasma acyl ghrelin in FD patients compared to control was significant only in male (15.9 fmol/mL vs 10.4 fmol/mL, P = 0.017). Significantly higher mRNA expressions of nerve growth factor and transient receptor potential vanilloid receptor 1 were observed in male (P = 0.002 and P = 0.014, respectively) than in female. In contrast, female FD patients had a higher anxiety and depression score than male FD (P = 0.029), and anxiety score was correlated with epigastric pain only in female FD patients (female: Spearman rho = 0.420, P = 0.037). The impairment of overall QoL was more prominent in female FD patients than male patients (5.4 ± 0.3 vs 6.5 ± 0.3, P = 0.020).
CONCLUSION Gender differences of ghrelin and nociception-related genes in male and psychological factors in female underlie FD symptoms. More careful assessment of psychological or emotional status is required particularly for the female FD patients.
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do 13620, South Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do 13620, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do 13620, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea
| | - Yong Sung Kim
- Department of Gastroenterology, Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi-do 1142, South Korea
| | - Sun Min Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do 13620, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do 13620, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea
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11
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Genetic variants of immune-related genes IL17F and IL10 are associated with functional dyspepsia: A case-control study. Indian J Gastroenterol 2017; 36:343-352. [PMID: 28965252 DOI: 10.1007/s12664-017-0788-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 09/11/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Low-grade inflammation may play an important role in pathogenesis of functional dyspepsia (FD). Since cytokines may influence gastric mucosal inflammation, which is associated with FD, we evaluated singe nucleotide polymorphisms (SNPs) of pro-inflammatory IL17F and anti-inflammatory IL10 cytokine genes in patients with FD and healthy subjects (HS). METHODS Two hundred and thirty-seven consecutive patients with FD (Rome III) and 250 HS were genotyped for IL17F (rs2397084: A/G, rs763780: T/C) and IL10 (rs1800896: G/A, rs1800871: C/T) (PCR-RFLP). RESULTS Patients with FD [173 (73%) men, age 38.4±12 years] were comparable with HS [195 (78%) men, age 37.3±12 years] with respect to age and gender. Out of 237 patients, 26 (11%) had epigastric pain, 55 (23.2%) had post-prandial distress syndromes (EPS, PDS), and 156 (65.8%) had EPS-PDS overlap. Among 237 patients with FD, GG (variant) genotype of IL17F (rs2397084) was more common than HS [15 (6.3%) vs. 4 (1.6%), p=0.015, odds ratio (OR)=4.0, 95% confidence interval (CI)=1.3-12.3]. IL17F (rs763780) and IL10 (rs1800896) were comparable among patients and HS (p=0.56, 0.28), respectively. However, TT (variant) genotype of IL10 (rs1800871) was more common among patients than HS [39 (16.5%) vs. 32 (12.8%), p=0.06, OR=1.7, 95% CI=0.98-2.98]. SNPs of IL17F and IL10 (rs2397084, rs763780, rs1800896 and rs1800871) were comparable among patients among sub-types of FD (p=0.80 and 0.44). CONCLUSION SNPs of IL17F (rs2397084) and IL10 (rs1800871) genes are associated with FD.
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12
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Choi YJ, Kim N, Yoon H, Shin CM, Park YS, Kim JW, Kim YS, Lee DH, Jung HC. Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses. J Gastroenterol Hepatol 2017; 32:1553-1561. [PMID: 28160607 DOI: 10.1111/jgh.13756] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 12/16/2016] [Accepted: 01/23/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS-FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS-FD. METHODS Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5-HTTLPR and ADRA2A 1291 G alleles and CCK-1R intron 779T>C were assessed using a multivariate logistic regression model. RESULTS A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS-FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non-overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS-FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS-FD overlap among FD patients. 5-HTTLPR L/L was a risk factor for the co-occurrence of IBS-C among FD patients (OR: 12.47; 95% CI: 2.00-77.75; P = 0.007). CONCLUSIONS Bloating was a risk factor for IBS-FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation-dominant IBS.
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong Sung Kim
- Department of Gastroenterology, Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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13
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Editorial: Functional Dyspepsia Treatment: Trials and Tribulations of Targeted Strategies. Am J Gastroenterol 2017; 112:910-912. [PMID: 28572654 DOI: 10.1038/ajg.2017.121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 03/14/2017] [Indexed: 12/11/2022]
Abstract
While functional dyspepsia (FD) is an exceedingly common disorder, the number of treatment options remains limited, and strategies for the individualized implementation of these therapies largely are lacking. In the current issue of American Journal of Gastroenterology, Saito and colleagues report on a secondary analysis of data from the Functional Dyspepsia Treatment Trial, specifically examining the role of two candidate genetic markers in predicting FD response to antidepressant treatments. Though the current study yielded a negative result, it nevertheless emphasizes the importance of our continued pursuit of therapeutic biomarkers in order to move beyond "one-size-fits-all" approaches to the treatment of FD and related disorders.
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Triantafyllou K, Kourikou A, Gazouli M, Karamanolis GP, Dimitriadis GD. Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms in the Greek population. Neurogastroenterol Motil 2017; 29. [PMID: 27430937 DOI: 10.1111/nmo.12913] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 06/27/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) susceptibility might be influenced by polymorphisms of genes related to inflammation (CD14, macrophage migration inhibitory factor [MIF]), motor (GNB3), and sensory dysfunction (GNB3, TRPV1). We examined the association between CD14 rs2569190, GNB3 rs5443, MIF rs222747, and TRPV1 rs755622 gene polymorphisms with FD (Rome III criteria) in the Greek population. METHODS We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41% Helicobacter pylori positive) and 181 controls using polymerase chain reaction-based methods and we measured disease symptoms' burden with a modified Gastrointestinal Symptoms Related Scale. KEY RESULTS Homozygous for the TT genotype and the T allele of the CD14 gene were significantly associated (OR [95% CI]) with FD (2.65 [1.42-4.94] and 1.67 [1.23-2.26], respectively). The CT, TT genotypes, and T allele frequencies of GNB3 showed also significant association with FD (2.18 [1.35-3.54], 3.46 [1.30-9.23], and 2.18 [1.48-3.19]). While heterozygous GC MIF genotype was more common in dyspeptics (1.67 [1.07-2.60]), homozygous CC genotype and the C allele of TRPV1 gene were more prevalent in controls (0.47 [0.25-0.87] and 0.69 [0.51-0.92], respectively). None of the gene polymorphism was related either to dyspepsia clinical syndrome type or to the H. pylori infection. Among dyspeptics, CD14 TT genotype was related to lower epigastric pain burden score (p<.011); CD14 CT genotype was related to higher epigastric burning and nausea burden scores (p<.04) while belching score was lower (p=.027) in MIF CG dyspeptics. CONCLUSION & INFERENCES Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms, while CD14 and MIF gene variants are also associated with dyspepsia symptoms burden.
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Affiliation(s)
- K Triantafyllou
- Hepatogastroenterology Unit, Second Department of Internal Medicine, Research institute and Diabetes Center, Attikon University General Hospital, Medical School, National and Kapodistrian University, Athens, Greece
| | - A Kourikou
- Hepatogastroenterology Unit, Second Department of Internal Medicine, Research institute and Diabetes Center, Attikon University General Hospital, Medical School, National and Kapodistrian University, Athens, Greece
| | - M Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University, Athens, Greece
| | - G P Karamanolis
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School, National and Kapodistrian University, Athens, Greece
| | - G D Dimitriadis
- Hepatogastroenterology Unit, Second Department of Internal Medicine, Research institute and Diabetes Center, Attikon University General Hospital, Medical School, National and Kapodistrian University, Athens, Greece
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15
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Lee SY, Masaoka T, Han HS, Matsuzaki J, Hong MJ, Fukuhara S, Choi HS, Suzuki H. A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients. Neurogastroenterol Motil 2016; 28:1401-8. [PMID: 27094759 DOI: 10.1111/nmo.12841] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 03/24/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. METHODS Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. KEY RESULTS Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). CONCLUSIONS & INFERENCES Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.
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Affiliation(s)
- S-Y Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - T Masaoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - H S Han
- Department of Pathology, Konkuk University School of Medicine, Seoul, Korea
| | - J Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - M J Hong
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - S Fukuhara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - H S Choi
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - H Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.,Medical Education Center, Keio University School of Medicine, Tokyo, Japan
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Increase in plasma acyl ghrelin levels is associated with abatement of dyspepsia following Helicobacter pylori eradication. J Gastroenterol 2016; 51:548-59. [PMID: 26412402 DOI: 10.1007/s00535-015-1124-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 09/13/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Ghrelin has been indicated as one of the etiological factors in functional dyspepsia (FD). METHODS We analyzed 179 patients with FD (based on the Rome III criteria) and 103 asymptomatic healthy individuals (controls) who had undergone endoscopy at Seoul National University Bundang Hospital from February 2011 to June 2014. FD patients were classified into three groups by means of a self-reported questionnaire: patients with postprandial distress syndrome (PDS; n = 49), patients with epigastric pain syndrome (EPS; n = 45), and patients with a combination of these two types (mixed group; n = 85). The fasting blood levels of acyl ghrelin and desacyl ghrelin and messenger RNA (mRNA) expression of preproghrelin in the fundic mucosa were measured by ELISAs and reverse transcription quantitative real-time PCR, respectively. One year after participant enrollment, they were measured again in 79 participants and the changes in the values were compared according to Helicobacter pylori eradication or symptom response. RESULTS Plasma acyl ghrelin level was lower in the PDS group than in the control and EPS groups (control group 14.1 fmol/mL, PDS group 8.9 fmol/mL, EPS group 13.8 fmol/mL, mixed group 11.3 fmol/mL; P = 0.003 and P = 0.012, respectively). One year after the eradication of H. pylori, plasma acyl ghrelin level was increased and gastric preproghrelin mRNA expression was upregulated (P = 0.004 and P < 0.001, respectively). Patients with abatement of symptoms demonstrated an increase in plasma acyl ghrelin level (from 11.51 to 21.00 fmol/L, P = 0.040). CONCLUSIONS Our results suggest that plasma acyl ghrelin plays a role in the development of PDS. H. pylori eradication upregulates preproghrelin mRNA expression and increases plasma acyl ghrelin level, contributing to the abatement of PDS symptoms.
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17
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Song YZ, You HY, Zhu ZH, Wen ZD, Xu HY, Chen BC, Chen ZJ, Huang QK. The C825T Polymorphism of the G-Protein β3 Gene as a Risk Factor for Functional Dyspepsia: A Meta-Analysis. Gastroenterol Res Pract 2015; 2016:5037254. [PMID: 27057160 PMCID: PMC4736015 DOI: 10.1155/2016/5037254] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2015] [Accepted: 11/16/2015] [Indexed: 12/17/2022] Open
Abstract
Background. Functional dyspepsia (FD) is a functional upper gastrointestinal disorder with significant morbidity and medical costs. Previous studies investigated the association of G-protein β3 (GNB3) genetic polymorphisms with FD but with inconsistent results. Therefore, we performed a meta-analysis to derive a precise estimation of the relationship between GNB3 polymorphisms and FD. Methods. We searched different databases including PubMed, EMBASE, CNKI, and the Ovid Library to gather eligible studies on GNB3 polymorphisms and FD. The association was assessed by the odds ratio (OR) with 95% confidence intervals (CI). Results. We identified 12 studies with 1109 cases and 2853 controls for the analysis. We found no associations of GNB3 C825T polymorphism with FD in the overall population (T versus C, OR = 1.06, 95% CI: 0.96-1.18, P = 0.26; TT versus CC + CT, OR = 1.16, 95% CI: 0.97-1.39, P = 0.11; TT + CT versus CC, OR = 1.01, 95% CI: 0.77-1.31, P = 0.96; TT versus CC, OR = 1.15, 95% CI: 0.93-1.44, P = 0.20). Subgroup analyses by genotyping method indicated that the magnitude of association was strengthened for additive model (OR = 1.15, 95% CI: 1.07-2.24, P = 0.02). Sensitivity analysis did not reveal significant associations under all models. Conclusions. This meta-analysis demonstrates that GNB3 C825T polymorphism may not be a risk factor for FD.
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Affiliation(s)
- Yi-Zuo Song
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - He-Yi You
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Zhe-Hui Zhu
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Zheng-De Wen
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Hui-Ying Xu
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Bi-Cheng Chen
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Zong-Jing Chen
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Qing-Ke Huang
- Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
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Oshima T, Tomita T, Ohda Y, Fukui H, Watari J, Miwa H. Epidemiology of Uninvestigated Dyspepsia and Functional Dyspepsia in Asia. J Gen Fam Med 2015. [DOI: 10.14442/jgfm.16.4_235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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"TRP inflammation" relationship in cardiovascular system. Semin Immunopathol 2015; 38:339-56. [PMID: 26482920 PMCID: PMC4851701 DOI: 10.1007/s00281-015-0536-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 10/08/2015] [Indexed: 02/07/2023]
Abstract
Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.
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20
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Kourikou A, Karamanolis GP, Dimitriadis GD, Triantafyllou K. Gene polymorphisms associated with functional dyspepsia. World J Gastroenterol 2015; 21:7672-7682. [PMID: 26167069 PMCID: PMC4491956 DOI: 10.3748/wjg.v21.i25.7672] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Revised: 04/07/2015] [Accepted: 05/21/2015] [Indexed: 02/06/2023] Open
Abstract
Functional dyspepsia (FD) is a constellation of functional upper abdominal complaints with poorly elucidated pathophysiology. However, there is increasing evidence that susceptibility to FD is influenced by hereditary factors. Genetic association studies in FD have examined genotypes related to gastrointestinal motility or sensation, as well as those related to inflammation or immune response. G-protein b3 subunit gene polymorphisms were first reported as being associated with FD. Thereafter, several gene polymorphisms including serotonin transporter promoter, interlukin-17F, migration inhibitory factor, cholecystocynine-1 intron 1, cyclooxygenase-1, catechol-o-methyltransferase, transient receptor potential vanilloid 1 receptor, regulated upon activation normal T cell expressed and secreted, p22PHOX, Toll like receptor 2, SCN10A, CD14 and adrenoreceptors have been investigated in relation to FD; however, the results are contradictory. Several limitations underscore the value of current studies. Among others, inconsistencies in the definitions of FD and controls, subject composition differences regarding FD subtypes, inadequate samples, geographical and ethnical differences, as well as unadjusted environmental factors. Further well-designed studies are necessary to determine how targeted genes polymorphisms, influence the clinical manifestations and potentially the therapeutic response in FD.
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