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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.

Salvi, Erika; Kutalik, Zoltán; Glorioso, Nicola; Benaglio, Paola; Frau, Francesca; Kuznetsova, Tatiana; Arima, Hisatomi; Hoggart, Clive; Tichet, Jean and Nikitin, Yury P, et al. (2012) In Hypertension 59(2). p.248-248
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... (More)
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. (Less)
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Hypertension
volume
59
issue
2
pages
248 - 248
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000299315800028
  • pmid:22184326
  • scopus:84856261411
ISSN
1524-4563
DOI
10.1161/HYPERTENSIONAHA.111.181990
language
English
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yes
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dbec98a7-561b-4c5c-a370-20b2b8264371 (old id 2273791)
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http://www.ncbi.nlm.nih.gov/pubmed/22184326?dopt=Abstract
date added to LUP
2012-01-03 20:45:56
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2017-11-19 03:04:34
@article{dbec98a7-561b-4c5c-a370-20b2b8264371,
  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.},
  author       = {Salvi, Erika and Kutalik, Zoltán and Glorioso, Nicola and Benaglio, Paola and Frau, Francesca and Kuznetsova, Tatiana and Arima, Hisatomi and Hoggart, Clive and Tichet, Jean and Nikitin, Yury P and Conti, Costanza and Seidlerova, Jitka and Tikhonoff, Valérie and Stolarz-Skrzypek, Katarzyna and Johnson, Toby and Devos, Nabila and Zagato, Laura and Guarrera, Simonetta and Zaninello, Roberta and Calabria, Andrea and Stancanelli, Benedetta and Troffa, Chiara and Thijs, Lutgarde and Rizzi, Federica and Simonova, Galina and Lupoli, Sara and Argiolas, Giuseppe and Braga, Daniele and D'Alessio, Maria C and Ortu, Maria F and Ricceri, Fulvio and Mercurio, Maurizio and Descombes, Patrick and Marconi, Maurizio and Chalmers, John and Harrap, Stephen and Filipovsky, Jan and Bochud, Murielle and Iacoviello, Licia and Ellis, Justine and Stanton, Alice V and Laan, Maris and Padmanabhan, Sandosh and Dominiczak, Anna F and Samani, Nilesh J and Melander, Olle and Jeunemaitre, Xavier and Manunta, Paolo and Shabo, Amnon and Vineis, Paolo and Cappuccio, Francesco P and Caulfield, Mark J and Matullo, Giuseppe and Rivolta, Carlo and Munroe, Patricia B and Barlassina, Cristina and Staessen, Jan A and Beckmann, Jacques S and Cusi, Daniele},
  issn         = {1524-4563},
  language     = {eng},
  number       = {2},
  pages        = {248--248},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Hypertension},
  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.},
  url          = {http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.181990},
  volume       = {59},
  year         = {2012},
}