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A multilocus approach to the antihypertensive pharmacogenetics of hydrochlorothiazide

Anke-Hilse Maitland-van der Zee1, Stephen T Turner, Gary L Schwartz

  • 1Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA. a.h.maitland-vanderzee@pharm.uu.nl

Pharmacogenetics and Genomics
|May 3, 2005
PubMed

Insights

Genetic variations in SCNN1G and endothelial nitric oxide synthase genes influence diastolic blood pressure response to hydrochlorothiazide, impacting hypertension treatment effectiveness.

Area of Science:

  • Pharmacogenetics
  • Cardiovascular Genetics
  • Hypertension Research

Background:

  • Essential hypertension is a common condition with variable treatment responses.
  • Hydrochlorothiazide is a widely used diuretic for hypertension management.
  • Inter-individual variability in drug response necessitates understanding genetic influences.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms in candidate genes and diastolic blood pressure (DBP) response to hydrochlorothiazide.
  • To identify specific gene variations that predict treatment efficacy in hypertensive patients.

Main Methods:

  • A community-based sample of 585 adults with essential hypertension was studied.
  • A nested case-control design compared high and low DBP responders after 4 weeks of hydrochlorothiazide monotherapy.
  • Genotyping for 45 polymorphisms in 19 candidate genes was performed, followed by set association and logistic regression analyses.

Main Results:

  • Two polymorphisms in the sodium channel gamma-subunit promotor gene (SCNN1G) and one in the endothelial nitric oxide synthase gene (eNOS) were significantly associated with DBP response.
  • The GA/GA haplotype of the SCNN1G gene showed a 5.21-fold increased odds of being a DBP responder.
  • The GG genotype of the ENOSA_rs1799983 polymorphism conferred a 2.19-fold increased odds of DBP response.

Conclusions:

  • Specific genetic variations in SCNN1G and eNOS are linked to differential odds of diastolic blood pressure response to hydrochlorothiazide.
  • These findings highlight potential pharmacogenetic markers for predicting hydrochlorothiazide efficacy.
  • Further research is required to elucidate the functional mechanisms underlying these pharmacogenetic effects.
Abstract

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