STK39 is a candidate gene for primary hypertension especially in women: results from 2 cohort studies in Swedes.

Background and Aim: As recently pinpointed by a genome wide association analysis the serine/threonine kinase 39 (STK39) gene is a possible candidate for hypertension. This kinase, also called Ste20-related proline-alanine rich kinase (SPAK), is strongly implicated in sodium reabsorption by the kidney through its modulator effect on furosemide and thiazide sensitive channels. Aim of our study was to test the effect of the functional STK39 rs35929607A>G polymorphism on blood pressure (BP) levels and hypertension prevalence and incidence in middle-aged Swedes participating to 2 urban-based survey in Malmö (Sweden). Methods: The rs35929607A>G polymorphism was genotyped in 5634 subjects included in the cardiovascular cohort of the Malmö Diet and Cancer (MDC-CVA) study and successively in 17690 participants of the Malmö Preventive project (MPP) both at baseline and at reinvestigation after a mean of 23 years. BP was measured by an auscultatory method and hypertension was considered as having BP values >= 140/90 mmHg or being under chronic antihypertensive treatment. Results: Both before and after adjustment for covariates in the MDC-CVA the rs35929607A>G polymorphism was associated with higher systolic and diastolic BP values in MDC-CVA but not in the MPP. In both surveys the polymorphism was associated with hypertension prevalence: after full adjustment using the autosomal dominant model the O.R. spanned between 1.071 to 1.151 with p < 0.05. After stratification for gender the results remained statistically significant in women but not in men. Conclusions: Our data confirm in 2 large cohort studies, a consistent association of the STK39 rs35929607A>G variant with hypertension, especially in women. Due to their pivotal role on sodium reabsorption at renal tubular level, SPAK could reveal to be a suitable target for antihypertensive therapy. The results on women deserve further deepening.