IL28B基因在HCV感染中的作用和应用前景.pdfVIP

HEREDITAS (Beijing) 2013 11 , 35(11): 1244―1252 ISSN 0253-9772 综 述 DOI: 10.3724/SP.J.1005.2013.01244 IL28B 基因在HCV 感染中的作用和应用前景 马柯, 张阿梅, 夏雪山 , 650500 丙型肝炎病毒(Hepatitis C virus, HCV)是造成慢性肝炎、肝硬化乃至肝癌的主要原因之一, 严重威胁人类 健康。宿主因素可影响HCV 的感染、治疗效果和自然清除率。近期, 欧美多个研究组对自愈和经过治疗的慢性 丙型肝炎患者进行了全基因组关联分析(Genome-wide association study, GWAS), 证明IL28B基因(编码IFN-λ3) 的 单核苷酸多态位点(Single nucleotide polymorphism, SNP)影响HCV 患者的治疗效果和自然清除率。IFN-λ3 通过 与其异源二聚受体IFN-λR1·IL-10R2 结合进行信号传导, 上调干扰素刺激基因的表达, 进而发挥抗病毒、抑制肿 瘤细胞生长以及免疫调节等生物学功能, 有望成为一种新型抗HCV 药物。虽然IL28B基因SNP影响病毒清除的机 制尚未清楚, 但其关联分析结果可作为HCV 患者临床治疗的辅助指导, 对HCV 患者进行IL28B 基因遗传易感和 功能研究将有助于该病的预防和治疗。 丙型肝炎; IL28B基因; 治疗效果; 自然清除率 The function and application of the IL28B gene in HCV infection and treatment MA Ke, ZHANG A-Mei, XIA Xue-Shan Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China Abstract: Hepatitis C virus (HCV) is the etiological factor for Hepatitis C, which is one of the most important patho- genic factors of chronic liver diseases, cirrhosis and even hepatocellular carcinoma. HCV infection brings great threat to human health. Host genetic background could impact HCV infection, viral clearance, and treatment. Recently, some ge- nome-wide association studies (GWAS) of HCV patients were performed. The results showed that single nucleotide poly- morphisms (SNPs) of the IL28B gene, which encodes protein IFN-λ3, are associated with viral clearance and treatment effectiveness of HCV patients who were cured by PEG-IFNα combined with ribavirin (RBV). IFN-λ3 interacts with its acceptor, a heterodimer (IF