Target Sequencing, Cell Experiments, and a Population Study Establish Endothelial Nitric Oxide Synthase (eNOS) Gene as Hypertension Susceptibility Gene (Articolo in rivista)

Type
Label
  • Target Sequencing, Cell Experiments, and a Population Study Establish Endothelial Nitric Oxide Synthase (eNOS) Gene as Hypertension Susceptibility Gene (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1161/HYPERTENSIONAHA.113.01428 (literal)
Alternative label
  • Erika Salvi (1), Tatiana Kuznetsova (7), Lutgarde Thijs (7), Sara Lupoli (1), Katarzyna Stolarz-Skrzypek (9), Francesca D'Avila (1), Valerie Tikhonoff (8), Silvia De Astis, Matteo Barcella (1), Jitka Seidlerová (10), Paola Benaglio (3), Sofia Malyutina (6), Francesca Frau (1), Dinesh Velayutham (1), Roberta Benfante (2), Laura Zagato (4), Alexandra Title, Daniele Braga (1), Diana Marek (3), Kalina Kawecka-Jaszcz (9), Edoardo Casiglia (8), Jan Filipovský (10), Yuri Nikitin (6), Carlo Rivolta (3), Paolo Manunta (4), Jacques S. Beckmann (3), Cristina Barlassina (1), Daniele Cusi (1), Jan A. Staessen (5) (2013)
    Target Sequencing, Cell Experiments, and a Population Study Establish Endothelial Nitric Oxide Synthase (eNOS) Gene as Hypertension Susceptibility Gene
    in Hypertension (Dallas Tex., 1979)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Erika Salvi (1), Tatiana Kuznetsova (7), Lutgarde Thijs (7), Sara Lupoli (1), Katarzyna Stolarz-Skrzypek (9), Francesca D'Avila (1), Valerie Tikhonoff (8), Silvia De Astis, Matteo Barcella (1), Jitka Seidlerová (10), Paola Benaglio (3), Sofia Malyutina (6), Francesca Frau (1), Dinesh Velayutham (1), Roberta Benfante (2), Laura Zagato (4), Alexandra Title, Daniele Braga (1), Diana Marek (3), Kalina Kawecka-Jaszcz (9), Edoardo Casiglia (8), Jan Filipovský (10), Yuri Nikitin (6), Carlo Rivolta (3), Paolo Manunta (4), Jacques S. Beckmann (3), Cristina Barlassina (1), Daniele Cusi (1), Jan A. Staessen (5) (literal)
Pagina inizio
  • 844 (literal)
Pagina fine
  • 852 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 62 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 9 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1) Department of Health Sciences and Graduate School of Nephrology, University of Milan; Division of Nephrology, San Paolo Hospital; and Genomic and Bioinformatics Unit, Filarete Foundation, Milan, Italy 2) Department of Medical Biotechnologies and Translational Medicine, University of Milan and CNR -Institute of Neuoscience, Milan, Italy 3) Department of Medical Genetics, University of Lausanne, Switzerland 4) Department of Nephrology and Dialysis, Università Vita Salute San Raffaele, Milan, Italy 5) Department of Epidemiology, Maastricht University, Maastricht, The Netherlands 6) Institute of Internal Medicine, Novosibirsk, Russian Federation 7) Studies Coordinating Centre, Division of Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium 8) Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy 9) First Department of Cardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland 10) Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic (literal)
Titolo
  • Target Sequencing, Cell Experiments, and a Population Study Establish Endothelial Nitric Oxide Synthase (eNOS) Gene as Hypertension Susceptibility Gene (literal)
Abstract
  • A case-control study revealed association between hypertension and rs3918226 in the endothelial nitric oxide synthase (eNOS) gene promoter (minor/major allele, T/C allele). We aimed at substantiating these preliminary findings by target sequencing, cell experiments, and a population study. We sequenced the 140-kb genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected with the eNOS promoter carrying either the T or the C allele, we quantified transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0% women; mean age 40.1 years), we studied blood pressure change and incidence of hypertension in relation to rs3918226, using multivariable-adjusted models. Sequencing confirmed rs3918226, a binding site of E-twenty six transcription factors, as the single nucleotide polymorphism most closely associated with hypertension. In T compared with C transfected cells, eNOS promoter activity was from 20% to 40% (P<0.01) lower. In the population, systolic/diastolic blood pressure increased over 7.6 years (median) by 9.7/6.8 mm Hg in 28 TT homozygotes and by 3.8/1.9 mm Hg in 2694 C allele carriers (P<=0.0004). The blood pressure rise was 5.9 mm Hg systolic (confidence interval [CI], 0.6-11.1; P=0.028) and 4.8 mm Hg diastolic (CI, 1.5-8.2; P=0.0046) greater in TT homozygotes, with no differences between the CT and CC genotypes (P>=0.90). Among 2013 participants normotensive at baseline, 692 (34.4%) developed hypertension. The hazard ratio and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24-3.37; P=0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter tags a hypertension susceptibility locus, TT homozygosity being associated with lesser transcription and higher risk of hypertension. (literal)
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