Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development
Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development
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人类白细胞抗原/DP-DQ 的遗传变异影响乙型肝炎病毒清除和肝细胞癌的发展
DOI：
10.1002/hep.24799
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发表时间：
2012-05-01
期刊：
影响因子：
13.5
通讯作者：
Hu, Zhibin
中科院分区：
文献类型：
--
作者：
Hu, Lingmin;Zhai, Xiangjun;Hu, Zhibin
最近的全基因组关联研究表明，人类白细胞抗原（HLA）-DP（rs3077和rs 9277535）和HLA-DQ（rs 2856718和rs7453920）中的4个单核苷酸多态性（SNP）与日本人群中的慢性B肝炎病毒（HBV）感染相关。超过75%的肝细胞癌（HCC）患者可归因于B型肝炎病毒（HBV）的持续感染，尤其是在中国。我们对来自中国东南部的1，300例HBV阳性HCC患者、1，344例持续性HBV携带者和1，344例HBV自然清除者进行了这四种SNP的基因分型，以进一步测试HLA-DP/DQ变异与HBV清除和HCC发展风险的相关性。Logistic回归分析显示，HLA-DQ rs 2856718显著降低宿主HCC风险，而三个SNP与HBV清除相关（HLA-DP rs 9277535以及HLA-DQ rs7453920和rs 2856718）。此外，当考虑多项检测调整时，HLA-DP rs3077对HBV持续感染和HCC发展的易感性显示出接近显著的影响。综上所述，我们首次报道了HLA-DP和HLA-DQ基因座的遗传变异可能是HBV清除和HCC发展风险的标志物SNP。（肝脏学2011）
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. (HEPATOLOGY 2011)