The incidence of hypertension in African Americans is nearly 50% higher than in Caucasians and is associated with higher rates of morbidity and mortality from stroke, heart failure, and end-stage renal disease. Studies are designed to identify genes that cosegregate with hypertension and with phenotypes associated with hypertension in African Americans. Both a genome wide search and a candidate gene approach will be used. To narrow genetic heteogeneity, we will identify 400 African American sib pairs, 18-55 years of age, who are hypertensive and also hypercholesterolemic. Extensive phenotyping of 200 of these sib pairs will be carried out to identify genetic loci of physiologic mechanisms that may contribute to hypertension. Phenotypic studies will evaluate renal function, renal and peripheral vascular reactivity, insulin sensitivity, and ion transport in erythrocytes. To determine if genes found to be associated with hypertension predict an increase of blood pressure, a cohort that is at risk for developing hypertension (normotensive sins from families of the 'affected' sins) will be genotype with repeat measurements of blood pressure in 3-4 years. Finally, DNA will be collected from 150 normotensive, normolipidemic African Americans for an association study (case control) for quantitative trait loci (QTL) which are found to cosegregate with hypertension in the affected sib pair study.
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