Multilocus effects of the renin-angiotensin-aldosterone system genes on blood pressure response to a thiazide diuretic

Background: The renin - angiotensin - aldosterone (RAA) system regulates blood pressure ( BP) levels and influences responses to antihypertensive medications. Variation in RAA system genes has been reported to influence interindividual differences in BP levels and the occurrence of hypertension (HTN). Methods: We evaluated the relationship between variation in genes of the RAA system and interindividual differences in BP response to a thiazide diuretic. Analyses were carried out in a race- and gender-specific manner in 255 unrelated hypertensive African-Americans ( 125 men and 130 women) and 246 unrelated hypertensive non-Hispanic Whites ( 133 men and 113 women). Results: The angiotensin II receptor ( AT(1)R) A1166C and angiotensinogen G-6A polymorphisms had a significant effect on systolic BP response to the diuretic in African-American women. Multilocus analyses indicated that the effects of these genes combined additively to influence response. Results of a permutation test to adjust for multiple comparisons and the possible nonindependence among genotypes remained significant at the P = 0.003 level. Conclusions: Among African-American women, particular gene variations in the RAA system have additive effects on BP response to a thiazide diuretic.