GENETICS OF ATHEROSCLEROSIS IN MEXICAN AMERICANS

该计划项目支持圣安东尼奥家庭之心 研究，第一个全面的遗传流行病学研究 墨西哥裔美国人的动脉粥样硬化及其相关性。它的目标是 检测和定位影响基因变异的新的多态基因 墨西哥人对心血管疾病的易感性 美国人。因为非胰岛素依赖型糖尿病 (NIDDM)和肥胖是心血管疾病的危险因素，在 这些人，糖尿病和肥胖症的多效性效应- 与心血管疾病数量相关的相关基因也将进行研究。 到本赠款期间结束时，有近1,400人 40多个墨西哥裔美国大家庭将成为 招募和考试。已经检测到了主要基因 影响高密度脂蛋白、低密度脂蛋白、胆固醇、载脂蛋白 AI(ApoAI)、apoB、三项与肥胖相关的指标(脂肪质量、身体 质量指数和生物耐药性指标)，两个与NIDDM相关的 特征(挑战后两小时胰岛素和糖尿病发病年龄)， 和两种荷尔蒙措施(性激素结合球蛋白和 脱氢表雄酮硫酸盐)。建议中的首要任务 授权期将是通过基因组来定位这些主要基因 搜索，使用强大的基于外显度和方差的分量 391个高度多态标记的基因分型分析 间隔大约10厘米的器官。在召回750个SAN中 安东尼奥家庭心脏研究参与者建议拨款 在此期间，将制定更完整的风险因素概况 测定与纤溶相关的定量表型 血栓形成和更接近动脉粥样硬化血管的表型 疾病终点将通过测量颈动脉壁来评估 厚度。将寻找主要基因的统计证据 定位对这些基因有实质性影响的基因的目标是 表型，使用相同的高度多态标记电池。 与特定染色体区域相关联的有力证据将 使用位置候选者方法进行追查。

This Program Project supports the San Antonio Family Heart Study, the first comprehensive genetic epidemiological study of atherosclerosis and its correlates in Mexican Americans. Its goal is to detect and map new polymorphic genes that influence variation in susceptibility to cardiovascular disease (CVD) in Mexican Americans. Because non-insulin-dependent diabetes mellitus (NIDDM) and obesity are risk factors for CVD and are common in this population, the pleiotropic effects of diabetes-and obesity- related genes on quantitative correlates of CVD also will be studies. By the end of the current grant period nearly 1,400 individuals in more than 40 extended Mexican American families will have been recruited and examined. Major genes already have been detected that influence HDL cholesterol, LDL, cholesterol, apolipoprotein AI (apoAI), apoB, three obesity-related measures (fat mass, body mass index, and an indicator of bioresistance), two NIDDM-related traits (two hour post-challenge insulin and diabetes age at onset), and two hormonal measures (sex hormone biding globulin an dehydroepiandrosterone sulfate). The first priority in the proposed grant period will be to map these major genes by genomic searching, using powerful penetrance-based and variance component analyses with genotypic data for 391 highly polymorphic markers spaced approximately 10 centimorgans apart. In a recall of 750 San Antonio Family Heart Study participants in the proposed grant period, a more complete risk factor profile will be developed by measuring quantitative phenotypes related to fibrinolysis and thrombosis, and phenotypes closer to the atherosclerotic vascular disease endpoint will be assessed by measuring carotid artery wall thickness. Statistical evidence for major genes will be sought with the goal of mapping genes that have substantial effects on these phenotypes, using the same battery of highly polymorphic markers. Strong evidence for linkage to a specific chromosomal region will be pursued using the positional candidate approach.