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

ObjectivesOur 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 methodsTwo 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.ResultsTwo 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.ConclusionOur findings suggest that hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.