Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response

Clin Biochem. 2011 Sep;44(13):1045-1049. doi: 10.1016/j.clinbiochem.2011.06.008. Epub 2011 Jun 17.

Abstract

Objectives: Our purpose was to investigate whether with-no-K[Lys] kinase (WNK) 1 and WNK4 genetic polymorphisms are associated with both hypertension and diuretics response.

Design and methods: Two WNK1 and one WNK4 polymorphisms were detected in two independent populations (n = 1592 and 602) for association with hypertension, and in two clinical trials of hydrochlorothiazide treatment (n = 542 and 274) for association with diuretics response.

Results: Two polymorphisms were found to be associated with hypertension risk with odds ratio of 1.55 for WNK1 rs1468326 (P<0.001) and 1.88 for WNK4 rs9916754 (P<0.001) in the first population, and 1.54 for WKN1 rs1468326, and 1.82 for WNK4 rs9916754 in the second population. However, two clinical trials found no relationship between these WNK polymorphisms and systolic/diastolic blood pressure responses to 4 or 8 weeks treatment of hydrochlorothiazide.

Conclusion: Our findings suggest that hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents
  • Blood Pressure / drug effects
  • Case-Control Studies
  • China
  • Diuretics / pharmacology*
  • Female
  • Humans
  • Hydrochlorothiazide / pharmacology*
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Hypertension / genetics*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Odds Ratio
  • Polymorphism, Genetic*
  • Protein Serine-Threonine Kinases / genetics*
  • WNK Lysine-Deficient Protein Kinase 1

Substances

  • Antihypertensive Agents
  • Diuretics
  • Intracellular Signaling Peptides and Proteins
  • Minor Histocompatibility Antigens
  • Hydrochlorothiazide
  • Protein Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • WNK1 protein, human
  • WNK4 protein, human