Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2017; 23(2): 232-241
Published online Jan 14, 2017. doi: 10.3748/wjg.v23.i2.232
Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virus-related hepatocellular carcinoma
Xiu-Ting He, Hong-Qin Xu, Xiao-Mei Wang, Xiu-Shu He, Jun-Qi Niu, Pu-Jun Gao
Xiu-Ting He, Department of Geriatrics, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Hong-Qin Xu, Xiao-Mei Wang, Jun-Qi Niu, Pu-Jun Gao, Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Xiu-Shu He, Department of Toxicology, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Author contributions: He XT, Niu JQ and Gao PJ designed the study, conducted all searches, appraised all potential studies and wrote and revised the draft manuscript and subsequent manuscripts; Niu JQ and Gao PJ are corresponding authors, they contributed equally to this article; Xu HQ and He XS collected and analyzed the data; Wang XM developed the study protocol; all authors have read and approved the final version of the manuscript to be published.
Supported by the National Science and Technology Major Project, No. 2014ZX10002002; the National Basic Research Program of China (973 Program), No. 2015CB554304; and the National Natural Science Foundation of China, No. 81373057 and No. 81301472.
Institutional review board statement: The study was reviewed and approved by the First Hospital of Jilin University, and Medical Ethics Committee of The First Hospital of Jilin University Approval For Clinical Trials (No. 2015-232).
Conflict-of-interest statement: All authors declared no conflict of interest related to this study.
Data sharing statement: No additional data are available.
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: Dr. Pu-Jun Gao, Vice Director, Department of Hepatology, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun 130021, Jilin Province, China. pujun-gao@163.com
Telephone: +86-431-88782729 Fax: +86-431-88782729
Received: August 21, 2016
Peer-review started: August 23, 2016
First decision: September 5, 2016
Revised: October 12, 2016
Accepted: October 31, 2016
Article in press: October 31, 2016
Published online: January 14, 2017
Abstract
AIM

To determine the relationship between five A3G gene single nucleotide polymorphisms and the incidence of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC).

METHODS

This association study was designed as a retrospective study, including 657 patients with chronic HBV infection (CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. Chronic HBV-infected patients recruited between 2012 and 2015 at The First Hospital of Jilin University (Changchun) were further classified into HBV-related HCC patients (n = 287) and non-HCC patients (n = 370). Frequency matching by age and sex was performed for each group. Human genomic DNA was extracted from whole blood. Gene polymorphisms were identified using a mass spectroscopic method.

RESULTS

There were no significant differences between the genotype and allele frequencies of the rs7291971, rs5757465 and rs5757463 A3G gene polymorphisms, and risk of CHB and HBV-related HCC. The AG genotype and G allele for rs8177832 were significantly related to a decreased risk of CHB (OR = 0.67, 95%CI: 0.47-0.96; OR = 0.69, 95%CI: 0.50-0.95, respectively) and HCC (OR = 0.53, 95%CI: 0.34-0.84; OR = 0.58, 95%CI: 0.39-0.87, respectively). A significant relationship was found between rs2011861 computed tomography, TT genotypes and increased risk of HCC (OR = 1.69, 95%CI: 1.02-2.80; OR = 1.82, 95%CI: 1.08-3.06, respectively). Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.

CONCLUSION

This study indicates that the A3G rs8177832 polymorphism is associated with a decreased risk of CHB infection and HCC, while the rs2011861 polymorphism is associated with an increased risk of HCC.

Keywords: Hepatitis B viral, Hepatocellular carcinoma, APOBEC3s, Polymorphism, Progression

Core tip: A3G is a dominant cytidine deaminase that strongly inhibits synthesis and editing of hepatitis B virus (HBV) DNA. We studied the relationship between five A3G gene single nucleotide polymorphisms and the incidence of chronic HBV infection (CHB) and hepatocellular carcinoma (HCC), including 657 CHB patients (287 HCC and 370 non-HCC) and 299 healthy controls. The AG genotype and G allele for rs8177832 were potentially protective factors against CHB and HCC. Computed tomography and TT genotypes of rs2011861 were risk factors for HCC. Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.