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Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.

Fava, Cristiano LU ; Danese, Elisa; Montagnana, Martina LU ; Sjögren, Marketa LU ; Almgren, Peter LU ; Engström, Gunnar LU ; Nilsson, Peter LU ; Hedblad, Bo LU ; Guidi, Gian C and Minuz, Pietro, et al. (2011) In Journal of Hypertension 29. p.484-491
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... (More)
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. CONCLUSION: 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. (Less)
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Journal of Hypertension
volume
29
pages
484 - 491
publisher
Lippincott Williams & Wilkins
external identifiers
  • WOS:000287236600014
  • PMID:21178783
  • Scopus:79951661537
ISSN
1473-5598
DOI
10.1097/HJH.0b013e328342b2c1
language
English
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yes
id
c6c8e4bf-41c0-4cb4-b530-0ce6b822d109 (old id 1755869)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21178783?dopt=Abstract
date added to LUP
2011-01-03 18:23:09
date last changed
2017-01-01 07:51:23
@article{c6c8e4bf-41c0-4cb4-b530-0ce6b822d109,
  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. CONCLUSION: 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.},
  author       = {Fava, Cristiano and Danese, Elisa and Montagnana, Martina and Sjögren, Marketa and Almgren, Peter and Engström, Gunnar and Nilsson, Peter and Hedblad, Bo and Guidi, Gian C and Minuz, Pietro and Melander, Olle},
  issn         = {1473-5598},
  language     = {eng},
  pages        = {484--491},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Hypertension},
  title        = {Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.},
  url          = {http://dx.doi.org/10.1097/HJH.0b013e328342b2c1},
  volume       = {29},
  year         = {2011},
}