GENETICS OF ATHEROSCLEROSIS IN MEXICAN AMERICANS

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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.