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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2018; 24(2): 248-256
Published online Jan 14, 2018. doi: 10.3748/wjg.v24.i2.248
Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection
Bui Tien Sy, Nghiem Xuan Hoan, Hoang Van Tong, Christian G Meyer, Nguyen Linh Toan, Le Huu Song, Claus-Thomas Bock, Thirumalaisamy P Velavan
Bui Tien Sy, Nghiem Xuan Hoan, Hoang Van Tong, Christian G Meyer, Nguyen Linh Toan, Le Huu Song, Thirumalaisamy P Velavan, Vietnamese-German Center of Excellence in Medical Research, Hanoi, Vietnam
Bui Tien Sy, Nghiem Xuan Hoan, Le Huu Song, Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi, Vietnam
Nghiem Xuan Hoan, Christian G Meyer, Claus-Thomas Bock, Thirumalaisamy P Velavan, Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
Hoang Van Tong, Nguyen Linh Toan, Thirumalaisamy P Velavan, Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
Claus-Thomas Bock, Department of Infectious Diseases, Robert Koch Institute, Berlin 13302, Germany
Author contributions: Velavan TP and Sy BT designed study; Sy BT, Tong HV and Hoan NX performed the experiments; Song LH, Toan NL and Hoan NX are involved in patient recruitment; Bock CT and Velavan TP contributed to study materials and consumables; Hoan NX, Tong HV and Sy BT performed the statistical analyses and interpreted the data; Hoan NX, Sy BT, Tong HV, Meyer CG and Velavan TP wrote the manuscript; Sy BT, Hoan NX and Tong HV contributed equally to this work.
Supported by NAFOSTED, No. 108.02-2017.15; and BMBF, No. 01DP17047.
Institutional review board statement: The study was approved by the institutional review board of the 108 Military Central Hospital and the 103 Military Hospital of the Vietnam Military Medical University, Hanoi, Vietnam.
Informed consent statement: Informed written consent was obtained after explanation of the study at the time of sampling from all participants.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Thirumalaisamy P Velavan, PhD, Professor, Molecular Genetics of Infectious Diseases, Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, Tübingen 72074, Germany.
velavan@medizin.uni-tuebingen.de
Telephone: +49-7071-2985981 Fax: +49-7071-294684
Received: October 16, 2017
Peer-review started: October 17, 2017
First decision: November 14, 2017
Revised: November 15, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: January 14, 2018
Processing time: 92 Days and 14.1 Hours
ARTICLE HIGHLIGHTS
Research background
Hepatitis B virus (HBV) infection is a major health concern in Vietnam. Investigations were carried out to determine IRF5 polymorphisms in the 3’ UTR region of the IFR5 locus on susceptibility to HBV infection and progression of liver diseases among clinically classified Vietnamese patients.
Research motivation
IRF5 is a particularly interesting member of the IRF family, which are crucial in the innate immune response with a variety of activities like activation of type I IFN genes, inflammatory cytokines and tumor suppressors. There are so far no data available on associations of IRF5 variants with susceptibility to HBV infection and the clinical course of HBV-related liver diseases.
Research objectives
This study aims to investigate possible effects of IRF5 polymorphisms on susceptibility to HBV infection and progression of liver diseases among clinically classified Vietnamese patients.
Research methods
The four IRF5 SNPs rs13242262A/T, rs77416878C/T, rs10488630A/G, and rs2280714G/A located closely at the 3′ downstream regions of the IRF5 locus were selected for this study. IRF5 variant genotyping was performed by direct sanger sequencing and by application of TaqMan® SNP genotyping assays.
Research results
Three hundred seventy-nine unrelated Vietnamese HBV-infected patients were randomly recruited in a case-control design. IRF5 variants are associated with LC progression in patients with CHB while the constructed haplotypes are associated with LC and HCC progression in CHB patients. In addition, IRF5 variants and their constructed haplotypes are associated with clinical outcomes of HBV infection.
Research conclusions
Host immune factors are crucial to the pathogenesis of HBV infection. For the first time the authors provide evidence of the functional role of human IRF5 in immune response to the clinical outcome of HBV infection. IRF5 variants rs13242262A/T and rs10488630A/G are associated with LC progression in patients with CHB. IRF5 haplotypes appear to influence the outcome of HBV infection.
Research perspectives
Further studies in this direction will provide insights into a role of IRF5 variants as prognostic markers of HBV-related liver diseases.
