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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus
Cliviany Borges da Silva, Diego Alves Vieira, Luisa Freitas de Melo, Anna Luiza Soares Chagas, Adriana Dias Gomes, César Lúcio Lopes de Faria Jr, Rosângela Teixeira, Dulciene Maria de Magalhães Queiroz, Gifone Aguiar Rocha, Maria Marta Sarquis Soares, Juliana Maria Trindade Bezerra, Luciana Diniz Silva
Cliviany Borges da Silva, Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
Cliviany Borges da Silva, Diego Alves Vieira, Luisa Freitas de Melo, Anna Luiza Soares Chagas, Rosângela Teixeira, Luciana Diniz Silva, Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
Diego Alves Vieira, Luisa Freitas de Melo, Anna Luiza Soares Chagas, Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
Adriana Dias Gomes, César Lúcio Lopes de Faria Jr, Dulciene Maria de Magalhães Queiroz, Gifone Aguiar Rocha, Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
Rosângela Teixeira, Luciana Diniz Silva, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
Maria Marta Sarquis Soares, Division of Endocrinology, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
Juliana Maria Trindade Bezerra, Epidemiology of Infectious and Parasitic Diseases Laboratory, Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
Author contributions: da Silva CB and Silva LD designed research (project conception, development of overall research plan, and study oversight); da Silva CB, Vieira DA, de Melo LF, Chagas ALS, Gomes AD, Faria Jr CLL conducted research (hands-on conduct of the experiments and data collection); Soares MMS, Teixeira R, Rocha GA and de Magalhães Queiroz DM provided essential reagents or provided essential materials; da Silva CB, de Bezerra JMT and Silva LD analysed data or performed statistical analysis; da Silva CB, de Bezerra JMT, Rocha GA and Silva LD wrote paper; da Silva CB, de Bezerra JMT, Rocha GA and Silva LD had primary responsibility for final content. All authors critically revised the manuscript, agree to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript.
Supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, No. APQ-02320-18.
Institutional review board statement: The protocol was approved by the Federal University of Minas Gerais Ethical Board (ETIC 0404.0.203.000-10).
Informed consent statement: The primary version (PDF) of the Informed Consent Form that has been signed by all subjects and investigators of the study, prepared in Portuguese was uploaded.
Conflict-of-interest statement: Authors declare no conflict of interests.
Data sharing statement: Technical appendix, statistical code and dataset available from the corresponding author at lucianadinizsilva@ufmg.br.
STROBE statement: The authors have read the STROBE statement-checklist of items and the manuscript was prepared and revised according to the strobe guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Luciana Diniz Silva, MD, PhD, Academic Research, Associate Professor, Attending Doctor, Research Scientist, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av Alfredo Balena 190 s/257, Belo Horizonte 30720030, Minas Gerais, Brazil. lucianadinizsilva@gmail.com
Received: December 29, 2019
Peer-review started: December 29, 2019
First decision: February 16, 2020
Revised: February 28, 2020
Accepted: March 22, 2020
Article in press: March 22, 2020
Published online: April 27, 2020
BACKGROUND
Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.
AIM
To investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients.
METHODS
Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models.
RESULTS
Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls (P = 0.81) and all alleles were in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001).
CONCLUSION
This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.
Core tip: Chronic hepatitis C is associated with type 2 diabetes mellitus. Previous studies have demonstrated associations between increased serum concentrations of Interleukin 6 (IL-6) and type 2 diabetes and advanced forms of liver disease. However, the role played by IL-6-174G/C single nucleotide polymorphism on the pathogenesis of hepatitis C virus-associated type 2 diabetes remains to be elucidated. To the best of our knowledge, this is the first study to demonstrate that the GC and GG genotypes of IL-6 are inversely associated with type 2 diabetes. We believe that our results may contribute to the understanding of the extra-hepatic manifestations in hepatitis C.
