Hypertension Clinical Trial
Official title:
Genes of Hypertension in African Americans
To identify genes contributing to hypertension in African Americans by focusing on the physiological pathways that determine arterial pressure.
BACKGROUND:
Since the mid 1990s, the investigators have extensively characterized African Americans for
phenotypes related to cardiovascular and renal function. Based on recently completed genome
scans, they have identified several chromosomal regions likely to contain genes influencing
hypertension-related phenotypes in hypertensive, African American sib pairs. For several
phenotypes, overlapping QTLs have also been identified in related studies in a genetically
isolated French Canadian population and/or in homologous chromosomal regions in the F2 cross
of Dahl-salt sensitive x normotensive Brown Norway rats.
DESIGN NARRATIVE:
The investigators will extensively phenotype 500 hypertensive and 500 normotensive African
American subjects to conduct a genetic association study, using a single nucleotide
polymorphism (SNP) genomic scan approach. To achieve a clear separation of blood pressures
from hypertensive subjects, normotensive subjects will be selected from the lower third of
the population-based blood pressure distribution. Hypertensive (BMI), and age. Inclusion of
phenotypes is based on their relevance to the pathophysiology of hypertension and prior
evidence of "heritability." Candidate genes for SNP analysis will be selected within
chromosomal regions of two quantitative trait loci (QTLs) that they have previously
demonstrated to be linked to hypertension-related phenotypes--a QTL for body mass index on
chromosome 1 and a QTL for microalbuminuria on chromosome 18. SNP analyses will be carried
out in 15 percent of the genes within each of these QTLs, and genes will be selected on the
basis of their relevance to hypertension, including documented sequence conservation for
blood pressure related QTLs with rat or mouse. The final goal of the project is to determine
if distinct clusters of blood pressure related phenotypes can be identified that will permit
stratification of hypertensive individuals into distinct subgroups to facilitate the
analysis of the genetic determinants of hypertension and/or provide mechanistic leads to
genes contributing to these traits.
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Observational Model: Case Control, Time Perspective: Cross-Sectional
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