title: HLA-DQ polymorphisms with HBV infection: different outcomes upon infection and prognosis to lamivudine therapy.
abstract: 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 Japanese patients. We tested the effects of the two single-nucleotide polymorphisms for all major HBV outcomes and lamivudine treatment in Han Chinese. 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 Han Chinese.
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shi Jiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Jia
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.forename: N
authors.initials: N
authors.lastname: Ma
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.forename: D
authors.initials: D
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D006683:HLA-DQ Antigens / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016896:Treatment Outcome
chemical_list: D006683:HLA-DQ Antigens; D019259:Lamivudine
keywords: HBV infection; HLA-DQ; lamivudine; polymorphisms