4.5 Article

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

Journal

HEPATOLOGY RESEARCH
Volume 47, Issue 8, Pages 755-766

Publisher

WILEY
DOI: 10.1111/hepr.12812

Keywords

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

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology (Japan)
  2. Ministry of Health, Labor, and Welfare (Japan) [H24-Kanen-Ippan-007]

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AimGenome-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. MethodsThe SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. ResultsIn 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), -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. ConclusionThis study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

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