Effects of endothelial nitric oxide synthase, α-adducin, and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide

Stephen T Turner, Arlene B. Chapman, Gary Lee Schwartz, Eric Boerwinkle

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Background: Pharmacogenetic discoveries may enable greater individualization of antihypertensive drug therapy. We investigated polymorphisms in the genes encoding endothelial nitric oxide synthase (Glu298→Asp), α-adducin (Gly460→Trp), the β 1-adrenoceptor (Arg389→Gly), β2-adrenoceptor (Arg16→Gly), and lipoprotein lipase (Ser447→Stop) for their potential influences on blood pressure (BP) response to a thiazide diuretic. Methods: The sample consisted of 291 unrelated non-Hispanic African American adults (150 women and 141 men) and 294 unrelated non-Hispanic white adults (126 women and 168 men) who were between 30 and 59.9 years of age and who had essential hypertension. Previous antihypertensive drug therapy was withdrawn for at least 4 weeks, and subjects were then treated with hydrochlorothiazide (25 mg daily) for 4 weeks to determine BP response. Results: The covariates of ethnicity, gender, age, and waist-to-hip ratio accounted for 26% of interindividual variation in systolic BP response and 11% of interindividual variation in diastolic BP response. After adjustment for covariates, the endothelial nitric oxide synthase Glu298→Asp polymorphism made an additional statistically significant contribution to predicting diastolic BP response to hydrochlorothiazide, accounting for another 1% of interindividual variation in response (P = .034). In contrast, the other polymorphisms, including the α-adducin Gly460→Trp polymorphism, made no statistically significant contributions to prediction of BP response. Conclusions: Although we reject the null hypothesis of no genetic effects on BP response to hydrochlorothiazide, the influence of variation at single sites is likely to be small. More extensive characterization of genetic variation is required for pharmacogenetic approaches to become clinically useful in tailoring antihypertensive drug therapy for individual patients.

Original languageEnglish (US)
Pages (from-to)834-839
Number of pages6
JournalAmerican Journal of Hypertension
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2003

Fingerprint

Hydrochlorothiazide
Nitric Oxide Synthase Type III
Blood Pressure
Genes
Antihypertensive Agents
Pharmacogenetics
Drug Therapy
Adrenergic Receptors
adducin
Sodium Chloride Symporter Inhibitors
Waist-Hip Ratio
Lipoprotein Lipase
African Americans

Keywords

  • Blood pressure
  • Diuretic
  • Genetics
  • Hypertension
  • Pharmacology
  • Polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{ac3cd0b18c514cb7bd20759e18ff014d,
title = "Effects of endothelial nitric oxide synthase, α-adducin, and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide",
abstract = "Background: Pharmacogenetic discoveries may enable greater individualization of antihypertensive drug therapy. We investigated polymorphisms in the genes encoding endothelial nitric oxide synthase (Glu298→Asp), α-adducin (Gly460→Trp), the β 1-adrenoceptor (Arg389→Gly), β2-adrenoceptor (Arg16→Gly), and lipoprotein lipase (Ser447→Stop) for their potential influences on blood pressure (BP) response to a thiazide diuretic. Methods: The sample consisted of 291 unrelated non-Hispanic African American adults (150 women and 141 men) and 294 unrelated non-Hispanic white adults (126 women and 168 men) who were between 30 and 59.9 years of age and who had essential hypertension. Previous antihypertensive drug therapy was withdrawn for at least 4 weeks, and subjects were then treated with hydrochlorothiazide (25 mg daily) for 4 weeks to determine BP response. Results: The covariates of ethnicity, gender, age, and waist-to-hip ratio accounted for 26{\%} of interindividual variation in systolic BP response and 11{\%} of interindividual variation in diastolic BP response. After adjustment for covariates, the endothelial nitric oxide synthase Glu298→Asp polymorphism made an additional statistically significant contribution to predicting diastolic BP response to hydrochlorothiazide, accounting for another 1{\%} of interindividual variation in response (P = .034). In contrast, the other polymorphisms, including the α-adducin Gly460→Trp polymorphism, made no statistically significant contributions to prediction of BP response. Conclusions: Although we reject the null hypothesis of no genetic effects on BP response to hydrochlorothiazide, the influence of variation at single sites is likely to be small. More extensive characterization of genetic variation is required for pharmacogenetic approaches to become clinically useful in tailoring antihypertensive drug therapy for individual patients.",
keywords = "Blood pressure, Diuretic, Genetics, Hypertension, Pharmacology, Polymorphism",
author = "Turner, {Stephen T} and Chapman, {Arlene B.} and Schwartz, {Gary Lee} and Eric Boerwinkle",
year = "2003",
month = "10",
day = "1",
doi = "10.1016/S0895-7061(03)01011-2",
language = "English (US)",
volume = "16",
pages = "834--839",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Effects of endothelial nitric oxide synthase, α-adducin, and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide

AU - Turner, Stephen T

AU - Chapman, Arlene B.

AU - Schwartz, Gary Lee

AU - Boerwinkle, Eric

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Background: Pharmacogenetic discoveries may enable greater individualization of antihypertensive drug therapy. We investigated polymorphisms in the genes encoding endothelial nitric oxide synthase (Glu298→Asp), α-adducin (Gly460→Trp), the β 1-adrenoceptor (Arg389→Gly), β2-adrenoceptor (Arg16→Gly), and lipoprotein lipase (Ser447→Stop) for their potential influences on blood pressure (BP) response to a thiazide diuretic. Methods: The sample consisted of 291 unrelated non-Hispanic African American adults (150 women and 141 men) and 294 unrelated non-Hispanic white adults (126 women and 168 men) who were between 30 and 59.9 years of age and who had essential hypertension. Previous antihypertensive drug therapy was withdrawn for at least 4 weeks, and subjects were then treated with hydrochlorothiazide (25 mg daily) for 4 weeks to determine BP response. Results: The covariates of ethnicity, gender, age, and waist-to-hip ratio accounted for 26% of interindividual variation in systolic BP response and 11% of interindividual variation in diastolic BP response. After adjustment for covariates, the endothelial nitric oxide synthase Glu298→Asp polymorphism made an additional statistically significant contribution to predicting diastolic BP response to hydrochlorothiazide, accounting for another 1% of interindividual variation in response (P = .034). In contrast, the other polymorphisms, including the α-adducin Gly460→Trp polymorphism, made no statistically significant contributions to prediction of BP response. Conclusions: Although we reject the null hypothesis of no genetic effects on BP response to hydrochlorothiazide, the influence of variation at single sites is likely to be small. More extensive characterization of genetic variation is required for pharmacogenetic approaches to become clinically useful in tailoring antihypertensive drug therapy for individual patients.

AB - Background: Pharmacogenetic discoveries may enable greater individualization of antihypertensive drug therapy. We investigated polymorphisms in the genes encoding endothelial nitric oxide synthase (Glu298→Asp), α-adducin (Gly460→Trp), the β 1-adrenoceptor (Arg389→Gly), β2-adrenoceptor (Arg16→Gly), and lipoprotein lipase (Ser447→Stop) for their potential influences on blood pressure (BP) response to a thiazide diuretic. Methods: The sample consisted of 291 unrelated non-Hispanic African American adults (150 women and 141 men) and 294 unrelated non-Hispanic white adults (126 women and 168 men) who were between 30 and 59.9 years of age and who had essential hypertension. Previous antihypertensive drug therapy was withdrawn for at least 4 weeks, and subjects were then treated with hydrochlorothiazide (25 mg daily) for 4 weeks to determine BP response. Results: The covariates of ethnicity, gender, age, and waist-to-hip ratio accounted for 26% of interindividual variation in systolic BP response and 11% of interindividual variation in diastolic BP response. After adjustment for covariates, the endothelial nitric oxide synthase Glu298→Asp polymorphism made an additional statistically significant contribution to predicting diastolic BP response to hydrochlorothiazide, accounting for another 1% of interindividual variation in response (P = .034). In contrast, the other polymorphisms, including the α-adducin Gly460→Trp polymorphism, made no statistically significant contributions to prediction of BP response. Conclusions: Although we reject the null hypothesis of no genetic effects on BP response to hydrochlorothiazide, the influence of variation at single sites is likely to be small. More extensive characterization of genetic variation is required for pharmacogenetic approaches to become clinically useful in tailoring antihypertensive drug therapy for individual patients.

KW - Blood pressure

KW - Diuretic

KW - Genetics

KW - Hypertension

KW - Pharmacology

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=0141674749&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141674749&partnerID=8YFLogxK

U2 - 10.1016/S0895-7061(03)01011-2

DO - 10.1016/S0895-7061(03)01011-2

M3 - Article

VL - 16

SP - 834

EP - 839

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 10

ER -