title: Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.
abstract: BACKGROUND
  As recently pinpointed by a genome-wide association study the serine/threonine kinase 39 (STK39) is a candidate gene for hypertension. This kinase is strongly implicated in sodium reabsorption by the kidney through its modulating effect on furosemide-sensitive and thiazide-sensitive channels. The aim of our study was to test the effects of the STK39 rs35929607A>G polymorphism on blood pressure (BP) levels and the prevalence and incidence of hypertension in middle-aged Swedes participating in two urban-based surveys in Malmö (Sweden).
  
  
  METHODS
  The rs35929607A>G polymorphism was genotyped in 5634 participants included in the cardiovascular cohort of the 'Malmö Diet and Cancer-cardiovascular arm' (MDC-CVA) study and successively in 17 894 participants of the 'Malmö Preventive Project' (MPP) both at baseline and at reinvestigation after a mean of 23 years. The effect of the same single nucleotide polymorphism on salt sensitivity was tested in 39 participants of the Salt Reduction to Avoid Hypertension study.
  
  
  RESULTS
  Both before and after adjustment for covariates, the functional rs35929607A>G polymorphism was associated with higher SBP and DBP values in the MDC-CVA, but not in the MPP. In both surveys, the polymorphism was associated with hypertension prevalence; after adjustment using the autosomal-dominant model, the odds ratio for hypertension ranged between 1.077 (MPP at baseline) and 1.151 (MDC-CVA) with P-value less than 0.05. After stratification for sex, the results remained statistically significant in women, but not in men. Carriers of the G-allele displayed an increase in salt sensitivity.
  
  
  CONCLUSIONS
  Our results from two large cohort studies support previous evidence about the association of the STK39 rs35929607A>G variant with hypertension, especially in women. If further confirmed in successive studies, owing to its pivotal role in sodium reabsorption at the renal tubule level, STK39 might prove to be a suitable target for antihypertensive therapy. The greater effect of the STK39 rs35929607A>G polymorphism in women with respect to men deserves further investigation.
authors.affiliation: Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. cristiano.fava@med.lu.se
authors.forename: Cristiano
authors.initials: C
authors.lastname: Fava
authors.forename: Elisa
authors.initials: E
authors.lastname: Danese
authors.forename: Martina
authors.initials: M
authors.lastname: Montagnana
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gian C
authors.initials: GC
authors.lastname: Guidi
authors.forename: Pietro
authors.initials: P
authors.lastname: Minuz
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015914:Estrogen Replacement Therapy; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012727:Sex Characteristics; D013548:Sweden
chemical_list: D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human