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.
Frazier
L
L
The University of Texas-Houston School of Nursing, Human Genetic Center and Institute of Molecular Medicine, Houston, TX, USA.
Turner
S T
ST
Schwartz
G L
GL
Chapman
A B
AB
Boerwinkle
E
E
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics; D001581:Benzothiadiazines; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D004232:Diuretics; D005260:Female; D005819:Genetic Markers / Q000502:physiology*; D014644:Genetic Variation / Q000502:physiology; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D044465:White People / Q000235:genetics
D001581:Benzothiadiazines; D004232:Diuretics; D005819:Genetic Markers; D044140:Receptor, Angiotensin, Type 1; D049993:Sodium Chloride Symporter Inhibitors; D000808:Angiotensinogen