title: Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development.
abstract: Recent genome-wide association studies showed that four single-nucleotide polymorphisms (SNPs) in human leukocyte antigen (HLA)-DP (rs3077 and rs9277535) and HLA-DQ (rs2856718 and rs7453920) were associated with chronic hepatitis B virus (HBV) infection in Japanese populations. More than 75% of hepatocellular carcinoma (HCC) patients are attributable to persistent infection of hepatitis B virus (HBV), especially in China. We genotyped these four SNPs in 1,300 HBV-positive HCC patients, 1,344 persistent HBV carriers, and 1,344 persons with HBV natural clearance from Southeast China to further test the associations of HLA-DP/DQ variants and with risk of both HBV clearance and HCC development. Logistic regression analyses showed that HLA-DQ rs2856718 significantly decreased host HCC risk, whereas three SNPs were associated with HBV clearance (HLA-DP rs9277535 as well as HLA-DQ rs7453920 and rs2856718). In addition, HLA-DP rs3077 showed an approaching significant effect on susceptibility to HBV persistent infection and HCC development when considering multiple testing adjustments. Taken together, we report, for the first time, that genetic variants in the HLA-DP and HLA-DQ loci may be marker SNPs for risk of both HBV clearance and HCC development.
authors: Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Lingmin
authors: L
authors: Hu
authors: Xiangjun
authors: X
authors: Zhai
authors: Jibin
authors: J
authors: Liu
authors: Minjie
authors: M
authors: Chu
authors: Shandong
authors: S
authors: Pan
authors: Jie
authors: J
authors: Jiang
authors: Yixin
authors: Y
authors: Zhang
authors: Hua
authors: H
authors: Wang
authors: Jianguo
authors: J
authors: Chen
authors: Hongbing
authors: H
authors: Shen
authors: Zhibin
authors: Z
authors: Hu
mesh_terms: D000328:Adult; D017677:Age Distribution; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution
chemical_list: D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens