Essential hypertension is a multifactorial disorder resulting from the interaction of heredity and environmental factor, but the genes responsible have not yet been defined. Previous studiesof candidate loci have given mixed results about the role of major genes in the development of hypertension. The reasons for this are unclear, but could be due to population differences, limitations of analytic methods, incorrect assumptions about animal models of the human disease, failure to account for gene-environment interactions, etc. This is a collaborative study involving the Howard University and Boston University Schools of Medicine. The racial mix at the Boston University Medical Center's clinics is expected to be 50% of Black descent and 50% Caucasians. In order to successfully carry out this project, we will collect blood samples, family histories, and clinical information from 50 kindreds with multiple living affected members and 500 affected sib-pairs, ascertained from several outpatient hypertension clinics affiliated with the Howard University Medical Center. We will collect blood specimens from these individuals for DNA analysis, to be performed at the SCOR Core Laboratory in Boston, until the Howard University DNA Analysis Laboratory is established. Data from normotensive control subjects will be available from the Framingham Heart Study and from the spouces in the hypertensive kindreds.
The Specific Aims of this proposal are: 1) To genotype the subjects from chromosomal loci, 2) To analyze the genetic marker data for linkage to hypertension, 3) To confirm positive linkages identified in aim #2 and to identify particular allele association in groups of hypertensive cases and normotensive controls using methods of linkage disequilibrium and DNA pooling, and 4) To screen for and assess mutations in candidate genes linked to hypertension in patients and controls.
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