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

L. Frazier, Stephen T Turner, Gary Lee Schwartz, A. B. Chapman, Eric Boerwinkle

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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 (AT1R) A1166C and angiotensinogen G6A 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.

Original languageEnglish (US)
Pages (from-to)17-23
Number of pages7
JournalPharmacogenomics Journal
Volume4
Issue number1
DOIs
StatePublished - 2004

Fingerprint

Sodium Chloride Symporter Inhibitors
Renin-Angiotensin System
Blood Pressure
African Americans
Genes
Angiotensinogen
Angiotensin Receptors
Diuretics
Antihypertensive Agents
Genotype
Hypertension

Keywords

  • African-americans
  • Diuretics
  • Gender
  • Genetics
  • Hypertension
  • Polymorphisms
  • RAA system

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Multilocus effects of the renin-angiotensin-aldosterone system genes on blood pressure response to a thiazide diuretic. / Frazier, L.; Turner, Stephen T; Schwartz, Gary Lee; Chapman, A. B.; Boerwinkle, Eric.

In: Pharmacogenomics Journal, Vol. 4, No. 1, 2004, p. 17-23.

Research output: Contribution to journalArticle

@article{73ee89e97ea64ce3a3bf30dc72c5bc0c,
title = "Multilocus effects of the renin-angiotensin-aldosterone system genes on blood pressure response to a thiazide diuretic",
abstract = "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 (AT1R) A1166C and angiotensinogen G6A 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.",
keywords = "African-americans, Diuretics, Gender, Genetics, Hypertension, Polymorphisms, RAA system",
author = "L. Frazier and Turner, {Stephen T} and Schwartz, {Gary Lee} and Chapman, {A. B.} and Eric Boerwinkle",
year = "2004",
doi = "10.1038/sj.tpj.6500215",
language = "English (US)",
volume = "4",
pages = "17--23",
journal = "Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Multilocus effects of the renin-angiotensin-aldosterone system genes on blood pressure response to a thiazide diuretic

AU - Frazier, L.

AU - Turner, Stephen T

AU - Schwartz, Gary Lee

AU - Chapman, A. B.

AU - Boerwinkle, Eric

PY - 2004

Y1 - 2004

N2 - 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 (AT1R) A1166C and angiotensinogen G6A 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.

AB - 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 (AT1R) A1166C and angiotensinogen G6A 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.

KW - African-americans

KW - Diuretics

KW - Gender

KW - Genetics

KW - Hypertension

KW - Polymorphisms

KW - RAA system

UR - http://www.scopus.com/inward/record.url?scp=1342289661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1342289661&partnerID=8YFLogxK

U2 - 10.1038/sj.tpj.6500215

DO - 10.1038/sj.tpj.6500215

M3 - Article

C2 - 14735111

AN - SCOPUS:1342289661

VL - 4

SP - 17

EP - 23

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

SN - 1470-269X

IS - 1

ER -