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

Erika Salvi, Tatiana Kuznetsova, Lutgarde Thijs, Sara Lupoli, Katarzyna Stolarz-Skrzypek, Francesca D'Avila, Valerie Tikhonoff, Silvia De Astis, Matteo Barcella, Jitka Seidlerova, Paola Benaglio, Sofia Malyutina, Francesca Frau, Dinesh Velayutham, Roberta Benfante, Laura Zagato, Alexandra Title, Daniele Braga, Diana Marek, Kalina Kawecka-JaszczEdoardo Casiglia, Jan Filipovsky, Yuri Nikitin, Carlo Rivolta, Paolo Manunta, Jacques S. Beckmann, Cristina Barlassina, Daniele Cusi, Jan A. Staessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Web of Science)


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
Original languageEnglish
Pages (from-to)844-852
Issue number5
Publication statusPublished - Nov 2013


  • blood pressure
  • endothelial nitric oxide synthase gene
  • hypertension
  • population science
  • target sequencing
  • transfection

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