Case Control Study
Copyright ©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
Abstract
AIM

To investigate possible effects of IRF5 polymorphisms in the 3’ UTR region of the IFR5 locus on susceptibility to hepatitis B virus (HBV) infection and progression of liver diseases among clinically classified Vietnamese patients.

METHODS

Four IFR5 SNPs (rs13242262A/T, rs77416878C/T, rs10488630A/G, and rs2280714T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B (CHB). n = 99; liver cirrhosis (LC), n = 131; hepatocellular carcinoma (HCC), n = 149] and in 242 healthy controls by direct sequencing and TaqMan real-time PCR assays.

RESULTS

Comparing patients and controls, no significant association was observed for the four IFR5 variants. However, the alleles rs13242262T and rs10488630G contributed to an increased risk of liver cirrhosis (LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients (OR = 2.1, 95%CI: 1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups (LC vs CHB: OR = 0.4, 95%CI: 0.2-0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P = 0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT, AST and bilirubin.

CONCLUSION

Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.

Keywords: Hepatitis B virus infection, Liver diseases, IRF5, IFR5 polymorphisms, IFR5 haplotypes

Core tip:IFR5 is expressed in immune cells and mediates Toll-like receptor signal transduction, playing a vital role in the induction of antiviral and inflammatory response. So far, multiple IFR5 single nucleotide polymorphisms have been shown to be associated with autoimmune diseases. This study investigated the effects of four IFR5 variants on susceptibility to hepatitis B virus (HBV) infection and liver disease outcomes in HBV infected patients. Two IFR5 variants (rs13242262, rs10488630) and constructed haplotypes (TCGT, TCAT) were associated with clinical outcomes suggesting that IFR5 variants may contribute to determine the pathogenesis of HBV infection.