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

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 the 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 HBV envelope 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 (p = 0.0481), γ-GTP (p = 0.0030) and NAs 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 BCP region (p = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (p < 0.0001), platelet (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 demonstrated an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels. This article is protected by copyright. All rights reserved.