GENETICS OF ATHEROSCLEROSIS IN MEXICAN AMERICANS

The long-term goal of this Program Project is to identify individual genes
that contribute to variation in susceptibility to coronary heart disease
(CHD) in Mexican Americans. Hispanics are the fastest growing minority
population in the United States and will soon be our largest minority
group. This population has a high prevalence of CHD and of other disorders
that adversely affect the lipoprotein profile, particularly non-insulin-
dependent diabetes mellitus (NIDDM) and obesity. Nevertheless, very few
genetic studies of intervening variables for CHD have been directed at this
population, and the relationships among CHD, NIDDM and obesity remain
poorly understood for any human population. This Program Project will focus on genes that influence the lipoprotein
profile in members of randomly ascertained Mexican-American families, with
particular emphasis on genetic effects on reverse cholesterol transport.
An overall objective is to investigate the pleiotropic effects of these
"lipoprotein genes" and their interactions with genes that affect NIDDM
antecedents and body fat distribution. The interactions of lipoprotein
genes with sex hormonal status and with environmental risk factors such as
diet, exercise, and smoking will be investigated. Genetic effects on
standard lipoprotein variables will be examined, e.g. plasma concentrations
of lipoproteins and apolipoproteins. Several novel lipoprotein phenotypes
also will be analyzed, e.g. amounts of esterified and unesterified
cholesterol and of specific apolipoproteins in lipoprotein subclasses.
Molecular, biochemical, and statistical genetic approaches will be used to
detect, localize and characterize genes that influence quantitative
phenotypes associated with lipoproteins, NIDDM, and obesity, and to
quantify the effects of known candidate loci on these phenotypes.