TNFSF/TNFRSF基因多态性及Th细胞免疫功能与HCV慢性化的分子流行病学研究

本研究结合现场流行病学、分子生物学、免疫学、生物统计学及相关技术方法，在中国高传播风险人群（吸毒者、血液透析者、有偿献血者）中，采用病例-对照、病例-病例研究设计，通过检测、分析比较HCV持续性感染者、HCV自限性清除者、健康对照者的TNFSF/TNFRSF单核苷酸多态性、免疫应答和环境及其他因素的异同，从分子和基因水平探讨HCV感染转归的影响因素，以宿主TNFSF/TNFRSF SNPs和丙肝转归的相关性为研究重点，包括宿主不同基因，及其与环境等影响因素，以及宿主基因、宿主免疫应答和环境影响因素三者的交互作用的特点和方式等。本研究旨在以综合多学科的现代流行病学，解决复杂传染病的病因学问题，同时深入探索HCV感染慢性化发生机理，有望对丙型肝炎这一重大公共卫生问题的群体、个体化防控提供工具、靶点及理论依据。

This study combines the technology of field epidemiology, molecular biology, immunology, biostatistics, using case-control, case-case study to explore the risk factors of chronic hepatitis C among Chinese high transmission risk population, including people who inject drugs (PWID), people receiving hemodialysis (HD) and paid blood donors (PBD). By detecting, comparing and analyzing the differences of TNFSF/TNFRSF gene polymorphism, immune state, environmental and other factors among persistent HCV infection group, spontaneous resolution group and un-infected controls, the risk factors for the outcomes of HCV infection will explore at the molecular level. In addition, this study focuses upon the relationship between TNFSF/TNFRSF gene and the outcomes of HCV infection, including the various host gene and environment, as well as the methods, intensity and characteristics of interaction between gene-gene, gene-environment and gene-immune -environment. In conclusion, this study aims to not only solve the problem of etiology of complicated infectious disease by using a comprehensive and multi-discipline modern epidemiology, but also explores the mechanisms of chronic hepatitis C. Therefore, it could provide the tool, target and theoretical foundation for the prevention and control of hepatitis C among population or individual.