SOCS-3基因多态性与CHC合并胰岛素抵抗的功能研究

慢性丙型肝炎(CHC)可引起胰岛素抵抗。研究提示，HCV核心蛋白可促进SOCS-3表达上调，诱发胰岛素抵抗。我们的前期研究提示，SOCS-3 rs4969170AA 基因型是胰岛素抵抗的危险因素之一。课题拟研究SOCS-3基因多态性与CHC合并胰岛素抵抗的关联性及致病机制:收集CHC合并胰岛素抵抗者300例，CHC非胰岛素抵抗者300例，健康人300例，检测SOCS-3 8个基因多态性位点的基因型，分析CHC诱发胰岛素抵抗的相关基因多态位点；根据关联分析的多态性位点按基因型结果分三组，每组60例，观察不同基因型对外周血单个核细胞SOCS-3 mRNA及蛋白表达、启动子转录活性、启动子与转录因子结合能力及所结合的不同转录因子的影响；分析三组基因型患者胰岛素受体底物-1/2与SOCS-3表达趋势的相关性，与胰岛素抵抗的关系，探讨SOCS-3基因多态性在CHC合并胰岛素抵中的作用机制。

Chronic Hepatitis C(CHC) induces insulin resistance (IR). There are evidences show that HCV core protein increases levels of suppressor of cytokine signaling 3 (SOCS-3).Our previous study suggested that SOCS-3 gene polymorphism rs4969170 AA genotype is associated with IR. This research will focus on study the polymorphisms of SOCS-3 and its mechanisms in the IR in CHC: 900 enrolled subjects, including 300 chronic hepatitis C patients with IR,300 patients without IR, and 300 healthy adults, will be genotyped for the eight SNPs of SOCS-3; We will evaluate the SOCS-3 mRNA and protein level in PBMCs according to three genotypes of the significant SNPs , 60 cases in every group; The effect of SOCS-3 on the promoter activity and the binding ability of transcription factor capacity with SOCS-3 promoter will be observed. Also, we observe the expression asociation of IRS-1/2 mRNA and protein with SOCS-3 expression in PBMCs. We will investigate the mechanisms of SOCS-3 polymorphisms in IR in CHC patients.