HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection

Yuka Ochi; Senju Hashimoto; Naoto Kawabe; Michihito Murao; Takuji Nakano; Toshiki Kan; Kazunori Nakaoka; Masashi Ohki; Takamitsu Kurashita; Tomoki Takamura; Sayuri Nomura; Toru Nishikawa; Aiko Fukui; Keisuke Osakabe; Naohiro Ichino; Kentaro Yoshioka

doi:10.1111/hepr.12812

HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection

Hepatol Res. 2017 Jul;47(8):755-766. doi: 10.1111/hepr.12812. Epub 2016 Oct 11.

Authors

Affiliations

¹ Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, Toyoake, Japan.
² Department of Clinical Pharmacy Practice and Health Care Management, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
³ Faculty of Medical Technology, School of Health Sciences, Fujita Health University, Toyoake, Japan.

PMID: 27580643
DOI: 10.1111/hepr.12812

Abstract

Aim: Genome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection.

Methods: The SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection.

Results: In 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core-related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ-glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild-type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels.

Conclusion: This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

Keywords: HBcrAg; HBeAg; HBsAg; HLA-DQ; hepatitis B virus; hepatocellular carcinoma.