About: Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene     Goto   Sponge   NotDistinct   Permalink

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  • 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 (PLESS-THAN OR EQUAL TO0.0004). 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 (PGREATER-THAN OR EQUAL TO0.90). 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.
  • 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 (PLESS-THAN OR EQUAL TO0.0004). 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 (PGREATER-THAN OR EQUAL TO0.90). 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. (en)
Title
  • Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene
  • Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene (en)
skos:prefLabel
  • Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene
  • Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene (en)
skos:notation
  • RIV/00216208:11140/13:10140208!RIV14-MSM-11140___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • R
http://linked.open...iv/cisloPeriodika
  • 5
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 109829
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11140/13:10140208
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • transfection; target sequencing; population science; hypertension; endothelial nitric oxide synthase gene; blood pressure (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [DA7595CD6C33]
http://linked.open...i/riv/nazevZdroje
  • Hypertension
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 62
http://linked.open...iv/tvurceVysledku
  • Filipovský, Jan
  • Casiglia, Edoardo
  • Kawecka-Jaszcz, Kalina
  • Kuznetsova, Tatiana
  • Malyutina, Sofia
  • Nikitin, Yuri
  • Staessen, Jan A.
  • Stolarz-Skrzypek, Katarzyna
  • Thijs, Lutgarde
  • Tikhonoff, Valerie
  • Manunta, Paolo
  • Benaglio, Paola
  • Frau, Francesca
  • Salvi, Erika
  • Mlíková Seidlerová, Jitka
  • Barcella, Matteo
  • Barlassina, Cristina
  • Beckmann, Jacques S.
  • Benfante, Roberta
  • Braga, Daniele
  • Cusi, Daniele
  • D'Avila, Francesca
  • De Astis, Silvia
  • Lupoli, Sara
  • Marek, Diana
  • Rivolta, Carlo
  • Title, Alexandra
  • Velayutham, Dinesh
  • Zagato, Laura
http://linked.open...ain/vavai/riv/wos
  • 000330110000020
issn
  • 0194-911X
number of pages
http://bibframe.org/vocab/doi
  • 10.1161/HYPERTENSIONAHA.113.01428
http://localhost/t...ganizacniJednotka
  • 11140
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