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Nature:Genetics:亚裔人群乙肝易感基因变异

更新时间:2009-07-26 08:47    作者:admin    文章来源:未知 点击次数: 2002
手机版地址:Nature:Genetics:亚裔人群乙肝易感基因变异

慢性乙肝是一种由乙肝病毒导致的最常见的肝脏疾病。现在,科学家们在亚洲人群中鉴别出与持续性乙肝病毒感染风险相关的基因变异,这一最新的研究成果发表在日前在线出版的《自然—遗传学》期刊上。

Yasuke Nakamura和同事实施了一组亚洲人群相关性研究,鉴别出慢性乙肝与含有HLA—DpA1和HLA—DPB1基因的一段基因组区域中11个遗传变性的重要相关性。这些基因在结构上类似于编码某种蛋白质的基因,这些蛋白质与对付乙肝病毒的免疫反应的启动密切相关。

据估计,全球约有4亿人口被传染上乙肝病毒,将近60%的肝癌与慢性乙肝和肝硬化有关。因为暴露于乙肝病毒后的临床结果有相当高的差异性,因此,鉴别出遗传变异和环境因素与乙肝病毒所导致疾病的进展的关系非常重要。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature Genetics 41, 591 - 595 (2009) 6 April 2009 | doi:10.1038/ng.348

A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians

Yoichiro Kamatani1,2, Sukanya Wattanapokayakit3, Hidenori Ochi4,5, Takahisa Kawaguchi4, Atsushi Takahashi4, Naoya Hosono4, Michiaki Kubo4, Tatsuhiko Tsunoda4, Naoyuki Kamatani4, Hiromitsu Kumada6, Aekkachai Puseenam7, Thanyachai Sura7, Yataro Daigo1,2, Kazuaki Chayama4,5, Wasun Chantratita8, Yusuke Nakamura1,4 p; Koichi Matsuda1

Chronic hepatitis B is a serious infectious liver disease that often progresses to liver cirrhosis and hepatocellular carcinoma; however, clinical outcomes after viral exposure vary enormously among individuals1. Through a two-stage genome-wide association study using 786 Japanese chronic hepatitis B cases and 2,201 controls, we identified a significant association of chronic hepatitis B with 11 SNPs in a region including HLA-DPA1 and HLA-DPB1. We validated these associations by genotyping two SNPs from the region in three additional Japanese and Thai cohorts consisting of 1,300 cases and 2,100 controls (combined P = 6.34 10-39 and 2.31 10-38, OR = 0.57 and 0.56, respectively). Subsequent analyses revealed risk haplotypes (HLA-DPA1*0202-DPB1*0501 and HLA-DPA1*0202-DPB1*0301, OR = 1.45 and 2.31, respectively) and protective haplotypes (HLA-DPA1*0103-DPB1*0402 and HLA-DPA1*0103-DPB1*0401, OR = 0.52 and 0.57, respectively). Our findings show that genetic variants in the HLA-DP locus are strongly associated with risk of persistent infection with hepatitis B virus.

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