Essential hypertension is a common disorder that contributes to morbidity, mortality, and cost of health care, especially among African-Americans. although diuretics are commonly prescribed for treatment of hypertension, blood pressure decreases in response to diuretic therapy in some individuals but not in others. The proposed research will determine whether measured variation in genes coding for components of the renin-angiotensin-aldosterone (RAA) system predicts interindividual differences in blood pressure response to diuretic therapy in 300 hypertensive African-Americans and in 300 hypertensive non-Hispanic whites (total 600 individuals). The investigators will conduct a standardized clinical protocol in which hypertensive adults are treated with the diuretic hydrochlorothiazide, 25 mg/day, for four weeks. They will measure interindividual variation in five RAA system genes-- angiotensinogen, renin, angiotensin-1 converting enzyme, angiotensin-II receptor, and aldosterone synthase --to accomplish the following specific aims in each ethnic group.
Aim 1 : To determine whether variation in genes of the RAA system predicts interindividual differences in blood pressure response to diuretic therapy.
Aim 2 : To determine whether variation in genes of the RAA system predicts interindividual differences in baseline measures of the endocrine RAA system or response of these measures to diuretic therapy.
Aim 3 : To determine whether the predictive effects of variations in genes of the RAA system on blood pressure response to diuretic therapy detected in Aim 1 are mediated through their effects on baseline measures of the endocrine RAA system or response of these measures to diuretic therapy, detected in Aim 2. Results of the proposed research have the potential to identify genes contributing to the etiology of interindividual differences in blood pressure response to diuretic therapy in African-Americans and in non-Hispanic whites.
Showing the most recent 10 out of 28 publications
