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Genetic variants in human leukocyte antigen/DP‐DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development
Author(s) -
Hu Lingmin,
Zhai Xiangjun,
Liu Jibin,
Chu Minjie,
Pan Shandong,
Jiang Jie,
Zhang Yixin,
Wang Hua,
Chen Jianguo,
Shen Hongbing,
Hu Zhibin
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24799
Subject(s) - hepatocellular carcinoma , hepatitis b virus , single nucleotide polymorphism , human leukocyte antigen , immunology , hla dq , virology , hepatitis c virus , hepatitis b , virus , medicine , biology , antigen , genotype , haplotype , gene , genetics
Recent genome‐wide association studies showed that four single‐nucleotide polymorphisms (SNPs) in human leukocyte antigen ( HLA )‐ DP (rs3077and 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. (H EPATOLOGY 2011)