新疆维吾尔族、汉族非酒精性脂肪肝甘油三酯代谢基因常见、稀有变异的高通量测序筛选

项目名称： 新疆维吾尔族、汉族非酒精性脂肪肝甘油三酯代谢基因常见、稀有变异的高通量测序筛选

项目编号： No.81460120

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 蔡雯

作者单位： 新疆医科大学

项目金额： 42万元

中文摘要： 非酒精性脂肪性肝病是由于体内甘油三酯的异常沉积，与2型糖尿病、代谢综合征密切相关。甘油三酯分解降低是造成肝脏脂肪堆积导致脂肪肝的重要原因，甘油三酯分解相关基因多态性对NAFLD发病机制具有重要意义。PNPLA3、APOC3等甘油三酯代谢基因是调节甘油三酯分解代谢的重要因子，不同人群PNPLA3、ApoC3等基因多态性与NAFLD关联性仍存在较大争议。前期研究发现维吾尔族NAFLD患病率明显高于汉族，而汉族人群中NAFLD与甘油三酯代谢基因SNPs（rs2854116、rs2854117）具有相关性,但在维吾尔族人群中无显著的相关性。这些差异可能由群体特异性所导致。基于这些假说，本研究拟利用维吾尔族独特性遗传背景，从调控甘油三酯代谢通路基因多态性和稀有突变入手，采用高通量测序技术，筛查维吾尔族、汉族甘油三酯代谢通路基因多态性和稀有与NAFLD相关性，探讨NAFLD分子遗传机制。

中文关键词： 非酒精性脂肪性肝病；甘油三酯分解；高通量测序；脂肪营养蛋白；维吾尔族

英文摘要： Nonalcoholic fatty liver disease (NAFLD) is due to the abnormal deposition of triglycerides, and associated with obesity, type 2 diabetes, dyslipidemia, hypertension and other symptoms of metabolic syndrome. Individual differences in genetic background was the important mechanism of NAFLD, lower triglycerides decomposition was the important cause leading to the fatty liver, liver triglyceride decomposition related gene polymorphism was of great significance in the pathogenesis of NAFLD. PNPLA3, APOC3 was an important adjusted factor of triglyceride catabolism. The result still has considerable controversy APOC3 gene polymorphism with NAFLD relevance. Previous studies found that prevalence of NAFLD in Uyghur was significantly higher than that of the Han population, and Polymorphism of triglyceride metabolism genes were related with NAFLD in Chinese Han, but there was not relationship in Uyghur population. The differences maybe were caused by group differences. Based on the hypothesis, the study from polymorphism of triglyceride decomposition related genes and rare mutation, using the next generation sequencing technology to detect the correlation between NAFLD and the polymorphism of triglyceride decomposition related gene and rare mutation in Uyghur and Han Chinese population polymorphism, and explore NAFLD molecular genetic mechanism in order to provide important basis for prevention.

英文关键词： Non-alcoholic fatty liver disease;Triglycerides decomposition;the next generation sequencing;PNPLA3;Uyghur