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-Jaszcz; Edoardo Casiglia; Jan Filipovsky; Yuri Nikitin; Carlo Rivolta; Paolo Manunta; Jacques S. Beckmann; Cristina Barlassina; Daniele Cusi; Jan A. Staessen

doi:10.1161/HYPERTENSIONAHA.113.01428

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 journal › Article › Academic › peer-review

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

Original language	English
Pages (from-to)	844-852
Journal	Hypertension
Volume	62
Issue number	5
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.113.01428
Publication status	Published - Nov 2013

Keywords

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

Access to Document

10.1161/HYPERTENSIONAHA.113.01428

Cite this

Salvi, E., Kuznetsova, T., Thijs, L., Lupoli, S., Stolarz-Skrzypek, K., D'Avila, F., Tikhonoff, V., De Astis, S., Barcella, M., Seidlerova, J., Benaglio, P., Malyutina, S., Frau, F., Velayutham, D., Benfante, R., Zagato, L., Title, A., Braga, D., Marek, D., ... Staessen, J. A. (2013). Target Sequencing, Cell Experiments, and a Population Study Establish Endothelial Nitric Oxide Synthase (eNOS) Gene as Hypertension Susceptibility Gene. Hypertension, 62(5), 844-852. https://doi.org/10.1161/HYPERTENSIONAHA.113.01428

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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",

keywords = "blood pressure, endothelial nitric oxide synthase gene, hypertension, population science, target sequencing, transfection",

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

year = "2013",

month = nov,

doi = "10.1161/HYPERTENSIONAHA.113.01428",

language = "English",

volume = "62",

pages = "844--852",

journal = "Hypertension",

issn = "0194-911X",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "5",

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Salvi, E, Kuznetsova, T, Thijs, L, Lupoli, S, Stolarz-Skrzypek, K, D'Avila, F, Tikhonoff, V, De Astis, S, Barcella, M, Seidlerova, 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 2013, 'Target Sequencing, Cell Experiments, and a Population Study Establish Endothelial Nitric Oxide Synthase (eNOS) Gene as Hypertension Susceptibility Gene', Hypertension, vol. 62, no. 5, pp. 844-852. https://doi.org/10.1161/HYPERTENSIONAHA.113.01428

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AU - Salvi, Erika

AU - Kuznetsova, Tatiana

AU - Thijs, Lutgarde

AU - Lupoli, Sara

AU - Stolarz-Skrzypek, Katarzyna

AU - D'Avila, Francesca

AU - Tikhonoff, Valerie

AU - De Astis, Silvia

AU - Barcella, Matteo

AU - Seidlerova, Jitka

AU - Benaglio, Paola

AU - Malyutina, Sofia

AU - Frau, Francesca

AU - Velayutham, Dinesh

AU - Benfante, Roberta

AU - Zagato, Laura

AU - Title, Alexandra

AU - Braga, Daniele

AU - Marek, Diana

AU - Kawecka-Jaszcz, Kalina

AU - Casiglia, Edoardo

AU - Filipovsky, Jan

AU - Nikitin, Yuri

AU - Rivolta, Carlo

AU - Manunta, Paolo

AU - Beckmann, Jacques S.

AU - Barlassina, Cristina

AU - Cusi, Daniele

AU - Staessen, Jan A.

PY - 2013/11

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N2 - 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

AB - 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

KW - blood pressure

KW - endothelial nitric oxide synthase gene

KW - hypertension

KW - population science

KW - target sequencing

KW - transfection

U2 - 10.1161/HYPERTENSIONAHA.113.01428

DO - 10.1161/HYPERTENSIONAHA.113.01428

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SN - 0194-911X

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