Tobin, M. D., Raleigh, S. M., Newhouse, S., Braund, P., Bodycote, C. L., Ogleby, J., Cross, D., Gracey, J., Hayes, S., Smith, T., Ridge, C., Caulfield, M., Sheehan, N. A., Munroe, P. B., Burton, P. R. and Samani, N. J. (2005) Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population. Circulation. 112(22), pp. 3423-3429. 1524-4539.
| Item Type: | Article |
|---|---|
| Abstract: | 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. |
| Uncontrolled Keywords: | blood pressure; genetics; hypertension; kidney; risk factors |
| Subjects: | R Medicine > RC Internal medicine > RC666 Diseases of the circulatory (Cardiovascular) system > RC685 Hypertension |
| Creators: | Tobin, Martin D, Raleigh, Stuart M, Newhouse, S, Braund, P, Bodycote, Clare L, Ogleby, Jenny, Cross, Deborah, Gracey, Jay, Hayes, Saija , Smith, Terry, Ridge, Cathy, Caulfield, Mark, Sheehan, Nuala A, Munroe, Patricia B, Burton, Paul R and Samani, Nilesh J |
| Faculties, Divisions and Institutes: |
University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Centre for Physical Activity and Chronic Disease University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society > Sports, Exercise & Life Sciences Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences Research Centres > Centre for Health Sciences and Services Research Centres > Centre for Physical Activity and Life Sciences |
| Date: | 1 November 2005 |
| Date Type: | Publication |
| Page Range: | pp. 3423-3429 |
| Journal or Publication Title: | Circulation |
| Volume: | 112 |
| Number: | 22 |
| Language: | English |
| DOI: | https://doi.org/10.1161/CIRCULATIONAHA.105.555474 |
| ISSN: | 1524-4539 |
| Status: | Published / Disseminated |
| Refereed: | Yes |
| URI: | http://nectar.northampton.ac.uk/id/eprint/17 |
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