新疆不同民族代谢综合征患者胆固醇吸收关键基因的变异与功能

项目名称： 新疆不同民族代谢综合征患者胆固醇吸收关键基因的变异与功能

项目编号： No.U1403221

项目类型： 联合基金项目

立项/批准年度： 2015

项目学科： 管理科学

项目作者： 马依彤

作者单位： 新疆医科大学

项目金额： 215万元

中文摘要： 本项目结合新疆维吾尔族、哈萨克族、汉族人群不同遗传背景、饮食风俗习惯和心脑血管发病特征，抽样测定血浆脂蛋白等脂质水平，通过Ca：L比值评估饮食胆固醇吸收率，依据胆固醇吸收率分为极高、极低、正常三组，结合高通量基因测序与生物信息学分析，筛选胆固醇吸收关键基因单核苷酸变异（SNV）。对筛查获得的变异，在细胞、动物水平进行功能测定、分子机制研究；对频率较高的SNV，则结合危险因素进行基因变异分型与LDL-C、代谢综合征的关联研究；对频率较低或稀有变异，以基因为单位，统计功能性变异出现频率，考察其在代谢综合征病例组和对照组中分布，并进一步扩大样本量进行临床验证。本项目通过建立基因变异/功能测定、关联分析/代谢紊乱/疾病表型的研究系统，利用生化和分子生物学等手段探究相关基因多态性对胆固醇吸收和代谢综合征发生发展过程的生理病理作用，在基因/蛋白/环境多层次水平上阐析新疆不同民族代谢综合征发病机理

中文关键词： 代谢综合征；胆固醇代谢；；单核苷酸变异；；功能测定；；关联研究

英文摘要： Uygur/Kazakh/Han three ethnic populations in the Xinjiang have different genetic backgrounds, dietary habits, customs, cardiovascular and cerebrovascular clinical characteristics. the project aims to sampling determine the plasma lipoprotein and lipid levels, evaluate dietary cholesterol absorption rate by Ca:L ratio, based on the absorption rate of cholesterol, every ethnic population divided into a very high rate, very low rate, normal rate three groups, combined with high-throughput gene sequencing and bioinformatics analysis, screening.cholesterol absorption key gene single nucleotide variation (SNV). For nonsynonymous variation, functional assay and molecular mechanisms are conducted in cell and animal level; for higher frequency SNV, combination of risk factors, association studies between gene mutation genotyping and LDL-C, metabolic syndromeare conducted; for lower frequency or rare variants, functional variant frequency of occurrence are calculated for one gene unit, and examine their distribution in the metabolic syndrome group and control group, and further expand the sample size for clinical validation. The project explore the related gene polymorphism in the absorption of cholesterol and pathophysiological role in the occurrence and development process of metabolic syndrome by establishment of genetic variation / function test and associated analysis / metabolic disorder / disease phenotype system and by means of biochemical and molecular biology, to explain pathogenesis of metabolic syndrome in the multi-layered level of the gene / protein / environment.

英文关键词： NULL