HLA - DP基因多态性影响慢性乙型肝炎病毒感染的结果

StephenW

HLA-DP Polymorphisms Affect the Outcomes of Chronic Hepatitis B Virus Infections, Possibly through Interacting with Viral Mutations

    Qi Zhanga,
    Jianhua Yina,
    Yuwei Zhanga,
    Yang Denga,
    Xiaowei Jia,
    Yan Dua,
    Rui Pua,
    Yifang Hana,
    Jun Zhaob,
    Xue Hanc,
    Hongwei Zhanga and
    Guangwen Caoa

- Author Affiliations

    Department of Epidemiology, Second Military Medical University, Shanghai, Chinaa
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, Chinab
    Division of Chronic Diseases, Center for Disease Control and Prevention of Yangpu District, Shanghai, Chinac

ABSTRACT

Genetic polymorphisms of HLA-DP have been associated with hepatitis B virus (HBV) persistence. We aimed to determine the effect of HLA-DP polymorphisms on the generation of HBV mutations and their interactions on the outcomes of HBV infection. rs3077, rs3135021, rs9277535, and rs2281388 were genotyped in 1,342 healthy controls, 327 HBV clearance subjects, and 2,736 HBV-positive subjects, including 1,108 hepatocellular carcinoma (HCC) patients, using quantitative PCR. HBV mutations were determined by sequencing. Multiplicative interactions of HLA-DP polymorphisms and viral mutations were assessed by multivariate logistic regression. rs3077 (from subjects with genotype CT combined with those from subjects with genotype TT [CT+TT] versus CC), rs3135021 (GA+AA versus GG), rs9277535 (GA+AA versus GG), and rs2281388 (CC versus CT+TT) significantly decreased HBV persistence. This effect was found only in genotype B HBV-infected subjects compared to HBV clearance subjects. HLA-DP polymorphisms promoting HBV clearance were associated with a lower prevalence of mutations increasing HCC risk (C1653T, T1674C/G, A1846T, G1896A and pre-S2 mutations and pre-S deletion in genotype C) and a higher prevalence of mutations decreasing HCC risk (G1652A, T1673C, T1674C, G1719T, G1730C, and G1799C in genotype B and A1727T in genotype C). Significant effects of viral mutations on cirrhosis and HCC were selectively evident in those with HLA-DP polymorphisms promoting HBV persistence. The interactions of C1653T, T1674C/G, and G1896A mutations with HLA-DP polymorphisms promoting HBV clearance significantly decreased cirrhosis risk. The interaction of rs9277535 AA with the T1674C/G or G1719T mutation in genotype C significantly decreased HCC risk. In conclusion, HLA-DP polymorphisms affect genotype B HBV clearance, regulate immune selection of viral mutations, and influence cirrhosis and HCC risks contributed by HBV mutations.
FOOTNOTES

        Received 27 July 2013.
        Accepted 27 August 2013.
    Address correspondence to Guangwen Cao, [email protected].

    Q.Z. and J.Y. contributed equally to this work.

StephenW

HLA - DP基因多态性影响慢性乙型肝炎病毒感染的结果，可能是通过与病毒突变互动

    齐Zhanga ，
    建华依娜，
    周雨薇Zhanga ，
    杨灯阿
    小伟佳，
    闫都锕
    芮噗呵
    一方花，
    月Zhaob ，
    薛HANC
    红卫Zhanga和
    何广文CAOA

- 作者所属机构

    流行病学教研室，上海第二军医大学，吃奶
    肝胆外科，东方肝胆外科医院，第二军医大学，上海， Chinab
    慢性疾病，疾病预防控制中心和预防，上海杨浦区， Chinac部

摘要

遗传多态性与HLA- DP已与B型肝炎病毒（HBV）的持久性。我们的目的是确定HLA - DP基因多态性的影响上一代的HBV基因突变和它们之间的相互作用对HBV感染的结果。 rs3077 ， rs3135021 ， rs9277535和rs2281388在1,342名健康对照， 327 HBV间隙科目，和2,736例HBV阳性者，其中包括1,108肝细胞癌（HCC ）患者进行基因分型，采用荧光定量PCR 。 HBV基因突变进行了测序。多因素logistic回归乘法HLA-DP基因多态性与病毒突变的相互作用进行了评估。 rs3077 （ CT基因型结合与TT基因型CT + TT与CC ）， rs3135021 （ GA + AA与GG） ， rs9277535 （ GA + AA与GG）和rs2281388 （ CC与CT + TT科目的科目）显着降低乙肝病毒的持久性。这种效应被发现，只有在B基因型HBV感染者，相比HBV间隙科目。 HLA-DP基因多态性均与促进HBV清除突变增加肝癌风险（ C1653T ， T1674C / G， A1846T ， G1896A和前S2突变和pre-S缺失C基因型）和突变降低肝癌的发病率较高的患病率较低风险（ G1652A ， T1673C ， T1674C ， G1719T ， G1730C ， B基因型和C基因型A1727T G1799C ） 。肝硬化和肝癌的病毒突变的显着影响，促进乙肝病毒的持久性与HLA-DP基因多态性选择性明显。 C1653T的相互作用， T1674C / G和G1896A突变与HLA - DP基因多态性促进HBV清除肝硬化的风险显着降低。 T1674C / G或C基因型G1719T突变rs9277535 AA的相互作用显着降低肝癌风险。总之， HLA -DP基因多态性影响B基因型HBV间隙，调节免疫选择的病毒突变和影响力贡献HBV突变的肝硬化和肝癌的风险。
脚注

        2013年7月27日收到的。
        2013年8月27日。
    地址对应到曹陈广文， [email protected] 。

    Q.Z.和J.Y.同样对这项工作作出了贡献。