Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence
Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence
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DOI：
10.1073/pnas.0602800103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Hill, Adrian V. S.
中科院分区：
文献类型：
--
作者：
Frodsham, Angela J.;Zhang, Lyna;Hill, Adrian V. S.
持续性B型肝炎病毒感染是肝细胞癌的一个主要危险因素，肝细胞癌是一些发展中国家最常见的癌症。高达95%的出生时感染者和15%的新生儿期后感染者未能清除B型肝炎病毒，导致全球约3.5亿持久携带者。通过在冈比亚家庭的全基因组扫描，我们已经确定了一个主要的易感基因位点作为染色体21 q22上的第11类细胞因子受体基因簇。这些基因中的两个，I型IFN受体基因IFN-AR 2和编码IL-10相关细胞因子（包括IFN-λ）的受体链的IL-10 RB基因的编码变化与病毒清除相关（单倍型P值= 0.0003），并且体外测定支持这些变体在受体信号传导中的功能作用。
Persistent hepatitis B virus infection is a major risk factor for hepatocellular carcinoma, the most frequent cancer in some developing countries. Up to 95% of those infected at birth and 15% of those infected after the neonatal period fail to clear hepatitis B virus, together resulting in approximate to 350 million persistent carriers worldwide. Via a whole genome scan in Gambian families, we have identified a major susceptibility locus as a cluster of class 11 cytokine receptor genes on chromosome 21q22. Coding changes in two of these genes, the type I IFN receptor gene, IFN-AR2, and the IL-10RB gene that encodes a receptor chain for IL-10-related cytokines including the IFN-lambda s, are associated with viral clearance (haplotype P value = 0.0003), and in vitro assays support functional roles for these variants in receptor signaling.