This Article Free upon publication Full Text Full Text (PDF) Data Supplement All Versions of this Article: 52/5/974    most recent HYPERTENSIONAHA.108.118414v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tobin, M. D. Articles by Burton, P. R. Search for Related Content PubMed PubMed Citation Articles by Tobin, M. D. Articles by Burton, P. R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene SNP UniGene Medline Plus Health Information Seniors' Health Related Collections Other etiology Epidemiology Genetics of cardiovascular disease

(Hypertension. 2008;52:974.)
© 2008 American Heart Association, Inc.

Original Articles

Common Variation in the WNK1 Gene and Blood Pressure in Childhood

The Avon Longitudinal Study of Parents and Children

Martin D. Tobin; Nicholas J. Timpson; Louise V. Wain; Susan Ring; Louise R. Jones; Pauline M. Emmett; Thomas M. Palmer; Andrew R. Ness; Nilesh J. Samani; George Davey Smith; Paul R. Burton

From the Departments of Health Sciences and Genetics (M.D.T., L.V.W., T.M.P., P.R.B.) and Cardiovascular Sciences (N.J.S.), University of Leicester, United Kingdom; and the Medical Research Council Centre for Causal Analyses in Translational Epidemiology (N.J.T., G.D.S.) and Departments of Social Medicine (S.R., L.R.J.), Community Based Medicine (P.M.E.), and Oral and Dental Science (A.R.N.), University of Bristol, Bristol, United Kingdom.

Correspondence to Martin D. Tobin, Genetic Epidemiology Group, Departments of Health Sciences and Genetics, Adrian Building, University of Leicester, Leicester LE1 7RH, United Kingdom. E-mail mt47{at}le.ac.uk

WNK1 gene variants have been associated with adult blood pressure. We aimed to investigate relationships between WNK1 variants and blood pressure, as well as blood pressure change with age, in a longitudinal childhood study. Associations between single nucleotide polymorphisms in WNK1 and blood pressure and the rate of blood pressure change between 7 and 11 years were examined in the Avon Longitudinal Study of Parent and Children Study (n=5326 for systolic blood pressure at 11 years). We observed associations (P<0.05) with diastolic blood pressure gradient with age for 33 of 82 typed and imputed polymorphisms, including polymorphisms in exons 4, 10, and 11 (rs10774466, rs1012729, and rs9804992). The minor allele (G) of rs1012729 (frequency: 25.6%) was associated with a gender-adjusted change in a diastolic blood pressure gradient of –0.11 mm Hg/y (95% CI: –0.20 to –0.03 mm Hg/y; P=0.0054). No associations were shown with the systolic blood pressure gradient. At age 11 years, 30 polymorphisms showed association (P<0.05) with systolic blood pressure, including variants in exons 4 and 10 (rs10774466 and rs1012729). Only 3 polymorphisms were associated with diastolic blood pressure at 11 years. In exploration of polymorphism-dietary cation interactions on systolic blood pressure at 11 years, 59 reached significance (P<0.05; 12.3 expected by chance), mostly (n=33) related to dietary calcium. The findings show that common intronic and exonic WNK1 variants are associated with diastolic blood pressure gradient from 7 to 11 years and with systolic blood pressure at 11 years. Our study suggests that previously reported effects of WNK1 variants on blood pressure are mediated via effects on the gradient of blood pressure change with age.

Key Words: blood pressure • WNK1 gene • childhood • ALSPAC • dietary calcium

This article has been cited by other articles:

				E. J. Hoorn, N. van der Lubbe, and R. Zietse The renal WNK kinase pathway: a new link to hypertension Nephrol. Dial. Transplant., April 1, 2009; 24(4): 1074 - 1077. [Full Text] [PDF]