IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy
IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy
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DOI：
10.1038/ng.447
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发表时间：
2009-10-01
期刊：
影响因子：
30.8
通讯作者：
George, Jacob
中科院分区：
文献类型：
--
作者：
Suppiah, Vijayaprakash;Moldovan, Max;George, Jacob
丙型肝炎病毒 (HCV) 感染世界上 3% 的人口。慢性 HCV 的治疗包括聚乙二醇化干扰素-α (PEG-IFN-α) 和利巴韦林 (RBV) 的组合。为了确定与 HCV 治疗反应相关的遗传变异，我们对 293 名患有基因 1 型慢性丙型肝炎的澳大利亚个体进行了一项全基因组关联研究，研究了 PEG-IFN-α/RBV 联合治疗的持续病毒学反应 (SVR)，并在由 555 名个体组成的独立复制队列中进行了验证。我们报告了编码白介素 28B（IL28B，也称为 IFN lambda 3；rs8099917 组合 P = 9.25 x 10(-9)，OR = 1.98，95% CI = 1.57-2.52）的基因区域内与 SVR 的关联。 IL28B 有助于病毒抵抗，并且已知会被干扰素和 RNA 病毒感染上调。这些数据表明宿主遗传学可能有助于预测药物反应，并且它们还支持研究 IL28B 在 HCV 治疗和 IFN-α 治疗的其他疾病中的作用。
Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFN lambda 3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.