Background-Selection of antihypertensive therapy is often empiric and use of genetic information to guide drug therapy selection holds future promise.

Background:The ratio of plasma aldosterone concentration to plasma renin activity (PRA) is considered the screening test of choice for primary aldosteronism. Uncertainty exists, however, regarding its diagnostic accuracy and the effects of antihypertensive drugs and dietary sodium balance on test characteristics. Methods: We measured PRA and aldosterone in 118 white adults [71 men and 47 women; mean (SD) age, 51 (7) years] with previously diagnosed essential hypertension. Measurements were made while individuals were on antihypertensive drug therapy, after a 2-week drug-free period, after 4 days of dietary sodium loading, and after acute furosemide diuresis. We measured 24-h urine aldosterone excretion and PRA on the 4th day of dietary sodium loading to establish the diagnosis of primary aldosteronism. ROC curves were constructed for ratios measured under each clinical condition, and likelihood ratios were determined for individuals on or off antihypertensive drug therapy. When measured on and off antihypertensive drug therapy, the 95% CIs for the optimum cutpoint for the ratio overlapped. Point estimates of sensitivity on and off therapy were 73% (95% CI, 50 -96%) and 87% (70 -100%), respectively, and specificities were 74% (65-83%) and

Abstract-The T allele of the C825T polymorphism of the gene encoding the ␤ 3 -subunit of G proteins has been associated with increased sodium-hydrogen exchange and low renin in patients with essential hypertension. To assess its association with blood pressure response to diuretic therapy, we measured the C825T polymorphism in 197 blacks (134 men, 63 women) and 190 non-Hispanic whites (76 men, 114 women) with essential hypertension (meanϮSD age 48Ϯ7 years), who underwent monotherapy with hydrochlorothiazide for 4 weeks. This interindividual variation in response is primarily due to pharmacodynamic, not pharmacokinetic, differences 3 and likely reflects variation in pathophysiological mechanisms that contribute to hypertension in individual patients. 4 It has long been suspected that interindividual variation in drug responses may be influenced by genetic factors. 5 Recently, a polymorphism (C825T) was described in exon 10 of the gene encoding the ␤ 3 -subunit of G proteins (GNB3), 6 and subsequently it was found to be associated with a shortened splice variant of the G␤ 3 -protein that gives rise to enhanced signal transduction via pertussis toxin-sensitive G proteins. 7 The C825T polymorphism was originally identified through studies of lymphoblasts, derived from whites with essential hypertension, in which sodium-proton antiport activity was increased as a consequence of enhanced G protein-dependent signal transduction in response to a variety of vasoactive and growthpromoting stimuli. 8 The present study was prompted by recently reported associations of the 825T allele with obesity 9 and with low plasma renin 10 that suggest that the 825T allele might also be associated with a volume-expanded, sodium-sensitive, and therefore diuretic-responsive form of hypertension. 11,12 Hence, our objective was to determine whether the C825T polymorphism predicts interindividual variation in blood pressure response to diuretic therapy among subjects with essential hypertension. We tested this hypothesis in a community and clinic-based biracial sample of hypertensive women and men undergoing monotherapy with a thiazide diuretic. Methods SampleThe sample consisted of 197 unrelated black adults (134 women, 63 men) from Atlanta, Ga, and 190 unrelated non-Hispanic white adults (76 women, 114 men) from Rochester Minn, aged 30 to 59.9 years with previously diagnosed hypertension who were participants in an ongoing study to identify predictors of blood pressure response to diuretic therapy. In Atlanta, study candidates were identified through lists of registered voters in Fulton and DeKalb counties (70%); outpatient medical clinics of Emory University Hospital, Grady Memorial Hospital, and the Atlanta Veterans Administration Hospital (15%); and other community sources, including churches and public media (15%). In Rochester, candidates were identified through the Rochester Epidemiology Project 13 and a diagnostic index maintained by the Mayo Clinic for all residents of Olmsted County. A letter was sent to potential subjects providi...

A systematic search reveals numerous predictors of BP response to a standard antihypertensive dose of hydrochlorothiazide. However, because the majority of inter-individual variation in SBP and DBP responses remains unexplained, there is considerable opportunity for future investigations to improve the ability to predict individual BP responses to antihypertensive drug therapy.