Skip Navigation


Human Molecular Genetics Advance Access originally published online on May 11, 2005
Human Molecular Genetics 2005 14(13):1805-1814; doi:10.1093/hmg/ddi187
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
14/13/1805    most recent
ddi187v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (19)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Newhouse, S. J.
Right arrow Articles by Munroe, P. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Newhouse, S. J.
Right arrow Articles by Munroe, P. B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study

Stephen J. Newhouse1, Chris Wallace1, Richard Dobson1, Charles Mein1, Janine Pembroke1, Martin Farrall2, David Clayton3, Morris Brown3, Nilesh Samani4, Anna Dominiczak5, John M. Connell5, John Webster6, G. Mark Lathrop7, Mark Caulfield1 and Patricia B. Munroe1,*

1Clinical Pharmacology and Barts and the London Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine, Charterhouse Square, London, UK, 2Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK, 3Clinical Pharmacology and the Cambridge Institute of Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK, 4Cardiology, University of Leicester, Glenfield Hospital, Leicester, UK, 5BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, UK, 6Medicine and Therapeutics, Aberdeen Royal Infirmary, Aberdeen, UK and 7Centre National de Genotypage, Evry, France

* To whom correspondence should be addressed at: Clinical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. Tel: +44 2078823410; Fax: +44 2078823408; Email: p.b.munroe{at}qmul.ac.uk

Received February 17, 2005; Revised April 6, 2005; Accepted May 5, 2005

Mutations in the WNK1 gene cause Gordon's syndrome, a rare Mendelian form of hypertension. We assessed whether common WNK1 variants might also contribute to essential hypertension (EH), a multifactorial disorder affecting >25% of the adult population worldwide. A panel of 19 single nucleotide polymorphisms (SNPs) spanning the gene was selected from public databases and was genotyped in 100 white European families to determine the pattern of linkage disequilibrium, haplotype structure and tagging SNPs for the WNK1 locus. Eight tagging SNPs were identified with 90% power to predict common WNK1 haplotypes and SNPs. Family-based association tests were used to test for association with EH and severity of hypertension in 712 severely hypertensive families from the MRC British Genetics of Hypertension study resource. No association was found between WNK1 polymorphisms or haplotypes with hypertension; however, one SNP rs1468326, located 3 kb from the WNK1 promoter, was found to be nominally associated with severity of hypertension, with both systolic blood pressure (BP) (Z=+2.24, P=0.025) and diastolic BP (Z=+1.99, P=0.046). We also found nominal support for association of one common WNK1 haplotype with increased systolic BP (Z=+1.91, P=0.053). This is the first study to perform haplotype association analysis of the WNK1 gene with EH. This finding of association between a SNP near the promoter region and the severity of hypertension suggests that increased expression of WNK1 might contribute to BP variability and susceptibility to EH similar to the mechanism of hypertension observed in Gordon's syndrome.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 NEJMHome page
M. A. Ikram, S. Seshadri, J. C. Bis, M. Fornage, A. L. DeStefano, Y. S. Aulchenko, S. Debette, T. Lumley, A. R. Folsom, E. G. van den Herik, et al.
Genomewide Association Studies of Stroke
N. Engl. J. Med., April 23, 2009; 360(17): 1718 - 1728.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
M. D. Tobin, N. J. Timpson, L. V. Wain, S. Ring, L. R. Jones, P. M. Emmett, T. M. Palmer, A. R. Ness, N. J. Samani, G. D. Smith, et al.
Common Variation in the WNK1 Gene and Blood Pressure in Childhood: The Avon Longitudinal Study of Parents and Children
Hypertension, November 1, 2008; 52(5): 974 - 979.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
C. Richardson and D. R. Alessi
The regulation of salt transport and blood pressure by the WNK-SPAK/OSR1 signalling pathway
J. Cell Sci., October 15, 2008; 121(20): 3293 - 3304.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
P. Manunta, G. Lavery, C. Lanzani, P. S. Braund, M. Simonini, C. Bodycote, L. Zagato, S. Delli Carpini, C. Tantardini, E. Brioni, et al.
Physiological Interaction Between {alpha}-Adducin and WNK1-NEDD4L Pathways on Sodium-Related Blood Pressure Regulation
Hypertension, August 1, 2008; 52(2): 366 - 372.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
A. C. B. Marcano, B. Burke, J. Gungadoo, C. Wallace, P. J Kaisaki, P. Y Woon, M. Farrall, D. Clayton, M. Brown, A. Dominiczak, et al.
Genetic association analysis of inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) variants with essential hypertension
J. Med. Genet., September 1, 2007; 44(9): 603 - 605.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
N. Glorioso, V. L.M. Herrera, P. Bagamasbad, F. Filigheddu, C. Troffa, G. Argiolas, E. Bulla, J. L. Decano, and N. Ruiz-Opazo
Association of ATP1A1 and Dear Single-Nucleotide Polymorphism Haplotypes With Essential Hypertension: Sex-Specific and Haplotype-Specific Effects
Circ. Res., May 25, 2007; 100(10): 1522 - 1529.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
P. B. Munroe, C. Wallace, M.-Z. Xue, A. C. B. Marcano, R. J. Dobson, A. K. Onipinla, B. Burke, J. Gungadoo, S. J. Newhouse, J. Pembroke, et al.
Increased Support for Linkage of a Novel Locus on Chromosome 5q13 for Essential Hypertension in the British Genetics of Hypertension Study
Hypertension, July 1, 2006; 48(1): 105 - 111.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. P. Blaustein, J. Zhang, L. Chen, and B. P. Hamilton
How does salt retention raise blood pressure?
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R514 - R523.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. Hadchouel, C. Delaloy, S. Faure, J.-M. Achard, and X. Jeunemaitre
Familial Hyperkalemic Hypertension
J. Am. Soc. Nephrol., January 1, 2006; 17(1): 208 - 217.
[Full Text] [PDF]

Home page
 CirculationHome page
H. Zhang and J. A. Staessen
Association of Blood Pressure With Genetic Variation in WNK Kinases in a White European Population
Circulation, November 29, 2005; 112(22): 3371 - 3372.
[Full Text] [PDF]

Home page
 CirculationHome page
M. D. Tobin, S. M. Raleigh, S. Newhouse, P. Braund, C. Bodycote, J. Ogleby, D. Cross, J. Gracey, S. Hayes, T. Smith, et al.
Association of WNK1 Gene Polymorphisms and Haplotypes With Ambulatory Blood Pressure in the General Population
Circulation, November 29, 2005; 112(22): 3423 - 3429.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.