Molecular Epidemiology of Essential Hypertension

To localize individual genes, called blood pressure quantitative trait genes \[BPQTGs\], which influence blood pressure levels in the population-at- large, and to determine if these genes are able to predict the occurrence of essential hypertension or coronary artery disease.

BACKGROUND: Essential hypertension reaches epidemic proportions among adults and is a significant risk factor for premature coronary artery disease \[CAD\] and stroke. The research to localize BPQTGs represents an initial step toward applying DNA information to early identification of at-risk individuals and understanding the complex relationships among blood pressure, essential hypertension, and coronary artery disease. DESIGN NARRATIVE: The study has four aims. Aim 1 uses robust sibling pair linkage methods, parental marker data, and office blood pressure levels measured on 1,376 full sibling pairs to localize BPQTGs to regions of the human genome marked by highly polymorphic tandem repeat loci in or very near to 59 genes involved in blood pressure regulation. These genes were selected based on their involvement in the renin/angiotensin system, ion transport, cardiac physiology, biometabolism of neurotransmitters, or carbohydrate and lipid metabolism. At each gene, a highly polymorphic tandem repeat marker locus has already been identified. Aim 2 uses methods of association analysis for related individuals and office blood pressure levels measured on 587 full sibships to localize BPQTGs to regions of the human genome marked by the 59 candidate BPQTGs. Aim 3 determines if variation in these BPQTGs improves the ability to predict differences in blood pressure levels in a sample of 1,166 unrelated normotensive adults or essential hypertension status in a sample of 1,160 unrelated grandparents beyond that provided by established predictors. Aim 4 determines if variation in these BPQTGs improves the ability to predict symptomatic or asymptomatic coronary artery disease status beyond that provided by established predictors including blood pressure and essential hypertension. Aims 3 and 4 also ask whether the predictive relationship of the traditional risk factors to blood pressure, essential hypertension, or coronary artery disease is different among genotypes at these BPQTGs. The study was renewed in FY 1999 to continue data analysis.