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Association of WNK1 Gene Polymorphisms and Haplotypes With Ambulatory Blood Pressure in the General Population

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journal contribution
posted on 09.12.2009, 16:16 by Martin D. Tobin, Stuart M. Raleigh, Stephen J. Newhouse, Peter S. Braund, Clare Bodycote, Jenny Ogleby, Deborah Cross, Jay Gracey, Saija Hayes, Terry Smith, Cathy Ridge, Mark J. Caulfield, Nuala A. Sheehan, Patricia B. Munroe, Paul R. Burton, Nilesh J. Samani
Background— Blood pressure (BP) is a heritable trait of major public health concern. The WNK1 and WNK4 genes, which encode proteins in the WNK family of serine-threonine kinases, are involved in renal electrolyte homeostasis. Mutations in the WNK1 and WNK4 genes cause a rare monogenic hypertensive syndrome, pseudohypoaldosteronism type II. We investigated whether polymorphisms in these WNK genes influence BP in the general population. Methods and Results— Associations between 9 single-nucleotide polymorphisms (SNPs) in WNK1 and 1 in WNK4 with ambulatory BP were studied in a population-based sample of 996 subjects from 250 white European families. The heritability estimates of mean 24-hour systolic BP (SBP) and diastolic BP (DBP) were 63.4% and 67.9%, respectively. We found statistically significant (P<0.05) associations of several common SNPs and haplotypes in WNK1 with mean 24-hour SBP and/or DBP. The minor allele (C) of rs880054, with a frequency of 44%, reduced mean 24-hour SBP and DBP by 1.37 (95% confidence interval, –2.45 to –0.23) and 1.14 (95% confidence interval, –1.93 to –0.38) mm Hg, respectively, per copy of the allele. Conclusions— Common variants in WNK1 contribute to BP variation in the general population. This study shows that a gene causing a rare monogenic form of hypertension also plays a significant role in BP regulation in the general population. The findings provide a basis to identify functional variants of WNK1, elucidate any interactions of these variants with dietary intake or with response to antihypertensive drugs, and determine their impact on cardiovascular morbidity and mortality.

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Citation

Circulation, 2005, 112 (22), pp. 3423-3429.

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VoR (Version of Record)

Published in

Circulation

Publisher

American Heart Association

issn

0194-911X

eissn

1524-4539

Copyright date

2005

Available date

09/12/2009

Publisher version

http://circ.ahajournals.org/content/112/22/3423

Language

en

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