<i><scp>HLA</scp>‐<scp>DQ</scp></i> polymorphisms with <scp>HBV</scp> infection: different outcomes upon infection and prognosis to lamivudine therapy

Abstract

Summary Two recent genome‐wide studies showed that the single‐nucleotide polymorphisms in the HLA ‐ DQ region (rs2856718 and rs9275572) were associated with chronic hepatitis B virus infection and chronic hepatitis C virus‐associated hepatocellular carcinoma in J apanese patients. We tested the effects of the two single‐nucleotide polymorphisms for all major HBV outcomes and lamivudine treatment in H an C hinese. A total of 1649 samples were enrolled, and peripheral blood samples were collected in this study. The single‐nucleotide polymorphisms in the HLA ‐ DQ region were genotyped using matrix‐assisted laser desorption/ionization time of flight mass spectrometry. Our study demonstrated the clear relevance of HLA ‐ DQ rs2856718 and rs9275572 with HBV susceptibility, natural clearance and HBV ‐associated HCC . HLA ‐ DQ rs2856718G and rs9275572A were strongly associated with decreased risk of chronic HBV infection (odds ratio = 0.641; P = 2.64 × 10 −4 ; odds ratio = 0.627, P = 7.22 × 10 −5 ) and HBV natural clearance (odds ratio = 0.610; P = 4.80 × 10 −4 ; odds ratio = 0.714, P = 0.013). Moreover, rs9275572A was also associated with development of cirrhosis and hepatocellular carcinoma (odds ratio = 0.632, P = 0.008). In addition, we showed for the first time to our knowledge that rs9275572 was a predictor for lamivudine therapy (viral response: odds ratio = 2.599, P = 4.43 × 10 −4 ; biochemical response: odds ratio = 2.279, P = 4.23 × 10 −4 ). Our study suggested that HLA ‐ DQ loci were associated with both HBV clearance and HBV ‐related diseases and outcomes of lamivudine treatment in H an C hinese.