To determine whether measured variation in genes coding for components of vasoconstriction
and volume regulating systems predict interindividual differences in blood pressure response
to therapy with a thiazide diuretic, hydrochlorothiazide, or an angiotensin II receptor
blocker, candesartan, in hypertensive African-Americans (N=300 treated with each drug) and
in hypertensive European Americans (N=300 treated with each drug).
Essential hypertension is a common disorder that contributes to morbidity, mortality, and
cost of health care, especially among African-Americans. Although a single-drug therapy is
commonly prescribed for treatment of hypertension, blood pressure levels are controlled in
some individuals but not in others. The study has the potential to identify genes
contributing to the etiology of interindividual differences in blood pressure response to
diuretic therapy in African-Americans and European Americans.
Hypertensive adults were treated with the diuretic hydrochlorothiazide, 25 mg/day, for four
weeks; or with the angiotensin II receptor blocker candesartan, 16 mg/day for 2 weeks
followed by 32 mg/day for 4 weeks. Interindividual variations in blood pressure responses
and in candidate genes coding for components of systems regulating vasoconstriction and
volume were measured. In addition, a panel of 500,000 single nucleotide polymorphisms
genome-wide was measured in subsets of the most extreme responders and nonresponders to each
drug for genome-wide association of analyses.
Primary (essential) hypertension