Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean.
Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean.
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DOI：
10.1371/journal.pone.0039175
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mizokami M
中科院分区：
文献类型：
--
作者：
Nishida N;Sawai H;Matsuura K;Sugiyama M;Ahn SH;Park JY;Hige S;Kang JH;Suzuki K;Kurosaki M;Asahina Y;Mochida S;Watanabe M;Tanaka E;Honda M;Kaneko S;Orito E;Itoh Y;Mita E;Tamori A;Murawaki Y;Hiasa Y;Sakaida I;Korenaga M;Hino K;Ide T;Kawashima M;Mawatari Y;Sageshima M;Ogasawara Y;Koike A;Izumi N;Han KH;Tanaka Y;Tokunaga K;Mizokami M
乙肝病毒感染可导致严重的肝脏疾病，包括肝硬变和肝细胞癌；然而，大约85%-90%的感染者成为非活跃携带者，生化持续缓解，患LC或肝癌的风险非常低。为了确定影响乙肝病毒清除的宿主遗传因素，我们利用来自乙肝病毒携带者和自发感染乙肝病毒的日本人和韩国人的样本，进行了全基因组关联研究和复制分析。日本和韩国的关联分析表明，Rs3077的Pmeta = 为1.89×10−12，rs9277542的Pmeta = 为9.69×10−10。我们还发现，在日本、韩国和包括中国人和泰国人在内的亚洲人群中，HLADPA1和HLADPB1基因对慢性乙型肝炎的保护作用显著相关(Rs3077的Pmeta = 为4.40×10−19，Rs9277542的Pmeta = 为1.28×10−15)。这些结果表明，在东亚人群中，人类白细胞抗原-DP基因座与抗持续乙肝病毒感染的保护作用和清除乙肝病毒之间的关联被广泛复制；然而，在高加索人或非洲人群中还没有关于GWAs的报道。基于本研究中的GWAS，没有显著的SNP与肝细胞癌的发生相关。为了阐明慢性乙型肝炎的发病机制和清除乙肝病毒的机制，还需要进一步的研究，包括对人类白细胞抗原-DP分子的功能分析。
Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85–90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with Pmeta = 1.89×10−12 for rs3077 and Pmeta = 9.69×10−10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (Pmeta = 4.40×10−19 for rs3077 and Pmeta = 1.28×10−15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.
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影响因子：
3.7
作者：
Wang L;Wu XP;Zhang W;Zhu DH;Wang Y;Li YP;Tian Y;Li RC;Li Z;Zhu X;Li JH;Cai J;Liu L;Miao XP;Liu Y;Li H
通讯作者：
Li H
影响因子：
3.7
作者：
Nishida N;Mawatari Y;Sageshima M;Tokunaga K
通讯作者：
Tokunaga K
影响因子：
4.6
作者：
Yano, Koji;Tamada, Yoko;Ishibashi, Hiromi
通讯作者：
Ishibashi, Hiromi
影响因子：
3.5
作者：
Miyagawa, Taku;Nishida, Nao;Tokunaga, Katsushi
通讯作者：
Tokunaga, Katsushi
影响因子：
12.7
作者：
SZMUNESS, W
通讯作者：
SZMUNESS, W