Genetic Epidemiology of Responses to Antihypertensives

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): Despite availability of multiple
antihypertensive drugs, which act on a variety of blood pressure-regulating
systems, less than 40 percent of treated hypertensive patients have their blood
pressures controlled. The overall objective of this research program is to
elucidate the genetic basis of interindividual variation in responses to
antihypertensive drug therapies. Such knowledge may reveal molecular mechanisms
contributing to hypertension and aid in the tailoring of more effective
antihypertensive drug therapy in individual patients. Blood pressure response
to a thiazide diuretic depends on initial reduction of intravascular fluid
volume due to inhibition of renal sodium reabsorption, and is subsequently
opposed by counterregulatory activities of the renin-angiotensin-aldosterone
system. Conversely, blood pressure response to an angiotensin H receptor
blocker depends on inhibition of the renin-angiotensin-aldosterone system and
is opposed by counterregulatory retention of sodium and fluid volume. In the
first cycle of this project, we found that variants of the genes encoding
angiotensin-converting enzyme and the G-proteins Beta3-subunit predicted blood
pressure response to a thiazide diuretic in hypertensive African-Americans (n =
300) and non-Hispanic whites (n = 300).

Aim 1 of this proposed renewal application will use the already-collected
samples to determine whether variation in additional genes encoding the
renin-angiotensin-aldosterone system, renal sodium transport systems, or
related modulators of vasoconstriction and volume predict interindividual
variation in blood pressure response to a thiazide diuretic. Aim 2 will
determine whether variation in these same genes predicts interindividual
variation in blood pressure response to an angiotensin II receptor blocker in
newly recruited hypertensive African-Americans (n = 300) and non-Hispanic
whites (n = 300). Aim 3 will use the combined samples from aims 1 and 2 (n=600
in each racial group) to contrast the identified predictors of response between
these two antihypertensive drugs that differentially target the balance of
vasoconstriction and volume maintaining blood pressure.
StatusFinished
Effective start/end date2/1/971/31/08

ASJC

  • Medicine(all)