hTERT基因多态性影响动脉粥样硬化形成机制及民族差异性研究

项目名称： hTERT基因多态性影响动脉粥样硬化形成机制及民族差异性研究

项目编号： No.81460326

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： 冯磊

作者单位： 昆明医科大学

项目金额： 47万元

中文摘要： 最新研究发现端粒缩短和端粒酶活性增高均是动脉粥样硬化（As）形成的重要危险因素。端粒长度由遗传因素和缩短速度决定，慢性炎症能引起端粒缩短，端粒酶除可延长端粒长度外，对维持端粒结构也起重要作用。hTERT是端粒酶关键限速成分，其基因多态性可影响hTERT蛋白合成，在激活端粒酶活性及功能中起关键作用。目前对hTERT基因多态性研究多集中在肿瘤的易感性上，未发现与As形成的相关性研究。前期研究首次在中国汉族人群中发现hTERT基因1号内含子rs2736100位点GG基因型As发生风险较高（OR=1.74），为本项目提供了理论依据。本研究将通过精细定位方法，扩大基因区域，增加人群数量，对云南主要民族人群进行研究和验证，了解不同民族人群差异。建立细胞模型，观察hTERT不同基因型及与炎症因子相互作用对转录水平和酶活性的影响，探寻hTERT基因多态性影响As形成的生物学机制，为As诊治新理论提供依据

中文关键词： 人端粒酶逆转录酶；单核苷酸多态性；动脉粥样硬化；炎症；民族

英文摘要： The latest studies showed that the activation of telomerase and marked telomere shortening were determined to be closely associated with the increasing severity of atherosclerosis(As). The telomere length of a species is determined by the heredity and frequency of cell division. Chronic inflammation can accelerate the telomere to shorten via increased cell division frequency, in the other hand, telomerase can not only lengthen telomere but also maintain the structure. As the key rate-limiting catalytic subunit of the telomerase enzyme, the single nucleotide polymorphism (SNP) of human telomerase reverse transcriptase (hTERT) can affect the activity and function of telomere. Now, the studies about the SNPs of hTERT are focused on the associated with susceptibility to different tumors, not been found in the association with As. In our early study, we have demonstrated for the first time that the GG Genotype of hTERT at genetic locus rs2736100 is associated with human As risk in the Han Chinese population（OR=1.74）.In order to confirm the theory, we are going to analysis and compare deeply in the chief ethnics of Yunnan through increasing cases and expanding genetic region by the method of Fine mapping, and reveal the distinguishing feature of different races. Through applying gene transfer technique to build cell model in human umbilical vein endothelial cells ( hUVECs ), we plan to observe how do the SNPs of hTERT and inflammation factors affect the reverse transcriptase and telomerase activity, and explore the development mechanism between the SNPs of hTERT with As .We hope the study can provide new scientific basis for the further prevention and treatment on As.

英文关键词： human telomerase reverse transcriptase;single-nucleotide polymorphism;atherosclerosis;inflammation;ethnic