Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2017; 23(9): 1602-1607
Published online Mar 7, 2017. doi: 10.3748/wjg.v23.i9.1602
Association between TLR7 copy number variations and hepatitis B virus infection outcome in Chinese
Fang Li, Xu Li, Gui-Zhou Zou, Yu-Feng Gao, Jun Ye
Fang Li, Gui-Zhou Zou, Yu-Feng Gao, Jun Ye, Department of Infectious Disease, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
Xu Li, Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Author contributions: Li F, Gao YF and Ye J contributed to the literature search and the writing of the manuscript; Li X and Zou GZ contributed to the original idea, as well as the polishing and final proof of the manuscript.
Supported by National Natural Science Foundation of China, No. 81273142.
Institutional review board statement: This study was reviewed and approved by the Biomedical Ethics Committee of the Anhui Medical University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have no conflicts of interest to report.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at aaylixu@qq.com. Participants gave informed consent for data sharing.
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: Xu Li, Professor, Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 230022, Anhui Province, China. aaylixu@qq.com
Telephone: +86-0551-63869400 Fax: +86-0551-63869400
Received: September 21, 2016
Peer-review started: September 22, 2016
First decision: December 19, 2016
Revised: December 27, 2016
Accepted: January 17, 2017
Article in press: January 17, 2017
Published online: March 7, 2017
Processing time: 165 Days and 15.8 Hours
Abstract
AIM

To explore whether copy number variations (CNVs) of toll-like receptor 7 (TLR7) are associated with susceptibility to chronic hepatitis B virus (HBV) infection.

METHODS

This study included 623 patients (495 males and 128 females) with chronic hepatitis B virus infection (CHB) and 300 patients (135 females and 165 males) with acute hepatitis B virus infection (AHB) as controls. All CHB patients were further categorized according to disease progression after HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). Copy numbers of the TLR7 gene were measured using the AccuCopy method. χ2 tests were used to evaluate the association between TLR7 CNVs and infection type. P values, odds ratios, and 95% confidence intervals (CIs) were used to estimate the effects of risk.

RESULTS

Among male patients, there were significant differences between the AHB group and CHB group in the distribution of TLR7 CNVs. Low copy number of TLR7 was significantly associated with chronic HBV infection (OR = 0.329, 95%CI: 0.229-0.473, P < 0.001). Difference in TLR7 copy number was also found between AHB and CHB female patients, with low copy number again associated with an increased risk of chronic HBV infection (OR = 0.292, 95%CI: 0.173-0.492, P < 0.001). However, there were no significant differences in TLR7 copy number among the three types of chronic HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). In addition, there was no association between TLR7 copy number and titer of the HBV e antigen.

CONCLUSION

Low TLR7 copy number is a risk factor for chronic HBV infection but is not associated with later stages of disease progression.

Keywords: Toll-like receptor 7; Hepatitis B virus; Copy number variations; Gene susceptibility

Core tip: Differences in patient genetic backgrounds may influence the quality of the immune response and may result in different hepatitis B virus (HBV) infection outcomes. Toll-like receptor 7 (TLR7) is involved in the sensing of viruses and priming of the subsequent immune response. We investigated the association between copy number at the TLR7 locus and genetic susceptibility to chronic HBV infection. Comparison of individuals with chronic and acute HBV revealed that low TLR7 copy number was associated with chronic but not acute HBV in both males and females, though it was not associated with subsequent disease progression.