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因素。 它的目标是 检测和绘制新的多态性基因， 墨西哥人对心血管疾病（CVD）的易感性 美国人 因为非胰岛素依赖型糖尿病 （NIDDM）和肥胖是CVD的危险因素， 这个人群，糖尿病和肥胖的多效性 相关基因与CVD的定量相关性也将进行研究。 截至本赠款期结束时， 超过40个墨西哥裔美国家庭将被 招募和检查。 主要基因已经被发现 影响高密度脂蛋白胆固醇，低密度脂蛋白胆固醇，载脂蛋白 AI（apoAI）、apoB、三项肥胖相关指标（脂肪量、身体 质量指数和生物抗性指标），两个NIDDM相关 性状（攻毒后2小时胰岛素和糖尿病发病年龄）， 和两种激素测量（性激素结合球蛋白和 硫酸脱氢表雄酮）。建议中的第一个优先事项 赠款期间将通过基因组定位这些主要基因 搜索，使用强大的基于方差和方差分量 391个高度多态性标记的基因型分析 间隔大约10厘摩。 在召回750名圣 安东尼奥家庭心脏研究参与者在拟议的赠款 在此期间，将制定更完整的风险因素简介， 测量与纤维蛋白溶解相关的定量表型， 血栓形成和表型更接近动脉粥样硬化血管 将通过测量颈动脉壁来评估疾病终点 厚 主要基因的统计学证据将通过以下方法来寻找： 目标是绘制对这些基因有实质性影响的基因， 表型，使用相同的电池高度多态性标记。 与特定染色体区域连锁的强有力证据将 使用位置候选人方法进行。

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.