| Autor: |
Salvi E; Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, Campus Sint Rafaël, Kapucijnenvoer 35, Block D, Box 7001, BE-3000 Leuven, Belgium. jan.staessen@med.kuleuven.be., Kuznetsova T, Thijs L, Lupoli S, Stolarz-Skrzypek K, D'Avila F, Tikhonoff V, De Astis S, Barcella M, Seidlerová J, Benaglio P, Malyutina S, Frau F, Velayutham D, Benfante R, Zagato L, Title A, Braga D, Marek D, Kawecka-Jaszcz K, Casiglia E, Filipovsky J, Nikitin Y, Rivolta C, Manunta P, Beckmann JS, Barlassina C, Cusi D, Staessen JA |
| Jazyk: |
angličtina |
| Zdroj: |
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2013 Nov; Vol. 62 (5), pp. 844-52. Date of Electronic Publication: 2013 Sep 09. |
| DOI: |
10.1161/HYPERTENSIONAHA.113.01428 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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