WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic

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

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Single nucleotide polymorphisms (SNPs) in genes encoding or influencing renal sodium transport systems were investigated as potential predictors of blood pressure (BP) response to a thiazide diuretic. A sample of 585 adults with essential hypertension (30 to 59.9 years of age; 50% blacks; 47% women) were treated with hydrochlorothiazide for 4 weeks (25 mg daily, orally) to determine office BP responses. Ambulatory BP responses were measured in a subset of 228 subjects. After adjustment for ethnicity, sex, age, and waist-to-hip ratio, 3 SNPs in WNK1 (rs2107614, rs2277869, and rs1159744), encoding a lysine-deficient protein kinase that regulates thiazide-sensitive sodium-potassium cotransport, made statistically significant contributions to predicting ambulatory BP responses, accounting for 2% to 4% of variation in systolic and diastolic responses (P<0.05). SNPs in the β2-adrenoceptor (rs2400707) and the epithelial sodium channel γ-subunit (rs5723 and rs5729) were associated with similar magnitude of variation in ambulatory systolic BP response (P=0.028) or office diastolic BP response (P<0.05), respectively. However, SNPs evaluated in the furosemide-sensitive sodium-potassium chloride cotransporter, potassium inwardly rectifying channel, chloride channel, thiazide-sensitive sodium chloride cotransporter, epithelial sodium channel β-subunit, and the mineralocorticoid receptor were not associated with significant variation in ambulatory or office BP responses. Polymorphisms in genes regulating renal sodium transport, in particular WNK1, predict interindividual differences in antihypertensive responses to hydrochlorothiazide.

Original languageEnglish (US)
Pages (from-to)758-765
Number of pages8
JournalHypertension
Volume46
Issue number4
DOIs
StatePublished - Oct 2005

Keywords

  • Blood pressure
  • Diuretics
  • Genetics
  • Polymorphism

ASJC Scopus subject areas

  • Internal Medicine

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