Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

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Version: author
Serval ID
serval:BIB_7BFB71DF48D8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.
Journal
Hypertension
Author(s)
Salvi E., Kutalik Z., Glorioso N., Benaglio P., Frau F., Kuznetsova T., Arima H., Hoggart C., Tichet J., Nikitin Y.P., Conti C., Seidlerova J., Tikhonoff V., Stolarz-Skrzypek K., Johnson T., Devos N., Zagato L., Guarrera S., Zaninello R., Calabria A., Stancanelli B., Troffa C., Thijs L., Rizzi F., Simonova G., Lupoli S., Argiolas G., Braga D., D'Alessio M.C., Ortu M.F., Ricceri F., Mercurio M., Descombes P., Marconi M., Chalmers J., Harrap S., Filipovsky J., Bochud M., Iacoviello L., Ellis J., Stanton A.V., Laan M., Padmanabhan S., Dominiczak A.F., Samani N.J., Melander O., Jeunemaitre X., Manunta P., Shabo A., Vineis P., Cappuccio F.P., Caulfield M.J., Matullo G., Rivolta C., Munroe P.B., Barlassina C., Staessen J.A., Beckmann J.S., Cusi D.
ISSN
1524-4563 (Electronic)
ISSN-L
0194-911X
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
59
Number
2
Pages
248-255
Language
english
Abstract
Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.
Pubmed
Web of science
Open Access
Yes
Create date
21/12/2011 15:27
Last modification date
20/08/2019 14:37
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