Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: The SOPHIA study

Francesca Frau; Roberta Zaninello; Erika Salvi; Maria Francesca Ortu; Daniele Braga; Dinesh Velayutham; Giuseppe Argiolas; Giovanni Fresu; Chiara Troffa; Emanuela Bulla; Patrizia Bulla; Silvia Pitzoi; Daniela Antonella Piras; Valeria Glorioso; Martina Chittani; Giampaolo Bernini; Michele Bardini; Francesco Fallo; Lorenzo Malatino; Benedetta Stancanelli; Giuseppe Regolisti; Claudio Ferri; Giovanbattista Desideri; Giuseppe Antonio Scioli; Ferruccio Galletti; Angela Sciacqua; Francesco Perticone; Ezio Degli Esposti; Alessandra Sturani; Andrea Semplicini; Franco Veglio; Paolo Mulatero; Tracy A. Williams; Chiara Lanzani; Timo P. Hiltunen; Kimmo Kontula; Eric Boerwinkle; Stephen T. Turner; Paolo Manunta; Cristina Barlassina; Daniele Cusi; Nicola Glorioso

doi:10.2217/pgs.14.119

Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: The SOPHIA study

Francesca Frau, Roberta Zaninello, Erika Salvi, Maria Francesca Ortu, Daniele Braga, Dinesh Velayutham, Giuseppe Argiolas, Giovanni Fresu, Chiara Troffa, Emanuela Bulla, Patrizia Bulla, Silvia Pitzoi, Daniela Antonella Piras, Valeria Glorioso, Martina Chittani, Giampaolo Bernini, Michele Bardini, Francesco Fallo, Lorenzo Malatino, Benedetta StancanelliGiuseppe Regolisti, Claudio Ferri, Giovanbattista Desideri, Giuseppe Antonio Scioli, Ferruccio Galletti, Angela Sciacqua, Francesco Perticone, Ezio Degli Esposti, Alessandra Sturani, Andrea Semplicini, Franco Veglio, Paolo Mulatero, Tracy A. Williams, Chiara Lanzani, Timo P. Hiltunen, Kimmo Kontula, Eric Boerwinkle, Stephen T. Turner, Paolo Manunta, Cristina Barlassina, Daniele Cusi, Nicola Glorioso

Nephrology and Hypertension

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Background: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. Aim: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. Materials & methods: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. Results: We identified a peak of association in CAMK1D gene (rs10752271, effect size-5.5 ± 0.94 mmHg, p = 1.2 × 10^-8). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. Conclusion: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension. Original submitted 7 May 2014; Revision submitted 29 July 201.

Original language	English (US)
Pages (from-to)	1643-1652
Number of pages	10
Journal	Pharmacogenomics
Volume	15
Issue number	13
DOIs	https://doi.org/10.2217/pgs.14.119
State	Published - Oct 1 2014

Keywords

angiotensin II receptor blockers
genome-wide association analysis
genomics
hypertension
losartan
pharmacogenomics

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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Frau, F., Zaninello, R., Salvi, E., Ortu, M. F., Braga, D., Velayutham, D., Argiolas, G., Fresu, G., Troffa, C., Bulla, E., Bulla, P., Pitzoi, S., Piras, D. A., Glorioso, V., Chittani, M., Bernini, G., Bardini, M., Fallo, F., Malatino, L., ... Glorioso, N. (2014). Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: The SOPHIA study. Pharmacogenomics, 15(13), 1643-1652. https://doi.org/10.2217/pgs.14.119

Frau, F, Zaninello, R, Salvi, E, Ortu, MF, Braga, D, Velayutham, D, Argiolas, G, Fresu, G, Troffa, C, Bulla, E, Bulla, P, Pitzoi, S, Piras, DA, Glorioso, V, Chittani, M, Bernini, G, Bardini, M, Fallo, F, Malatino, L, Stancanelli, B, Regolisti, G, Ferri, C, Desideri, G, Scioli, GA, Galletti, F, Sciacqua, A, Perticone, F, Degli Esposti, E, Sturani, A, Semplicini, A, Veglio, F, Mulatero, P, Williams, TA, Lanzani, C, Hiltunen, TP, Kontula, K, Boerwinkle, E, Turner, ST, Manunta, P, Barlassina, C, Cusi, D & Glorioso, N 2014, 'Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: The SOPHIA study', Pharmacogenomics, vol. 15, no. 13, pp. 1643-1652. https://doi.org/10.2217/pgs.14.119

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title = "Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: The SOPHIA study",

abstract = "Background: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. Aim: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. Materials & methods: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. Results: We identified a peak of association in CAMK1D gene (rs10752271, effect size-5.5 ± 0.94 mmHg, p = 1.2 × 10-8). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. Conclusion: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension. Original submitted 7 May 2014; Revision submitted 29 July 201.",

keywords = "angiotensin II receptor blockers, genome-wide association analysis, genomics, hypertension, losartan, pharmacogenomics",

author = "Francesca Frau and Roberta Zaninello and Erika Salvi and Ortu, {Maria Francesca} and Daniele Braga and Dinesh Velayutham and Giuseppe Argiolas and Giovanni Fresu and Chiara Troffa and Emanuela Bulla and Patrizia Bulla and Silvia Pitzoi and Piras, {Daniela Antonella} and Valeria Glorioso and Martina Chittani and Giampaolo Bernini and Michele Bardini and Francesco Fallo and Lorenzo Malatino and Benedetta Stancanelli and Giuseppe Regolisti and Claudio Ferri and Giovanbattista Desideri and Scioli, {Giuseppe Antonio} and Ferruccio Galletti and Angela Sciacqua and Francesco Perticone and {Degli Esposti}, Ezio and Alessandra Sturani and Andrea Semplicini and Franco Veglio and Paolo Mulatero and Williams, {Tracy A.} and Chiara Lanzani and Hiltunen, {Timo P.} and Kimmo Kontula and Eric Boerwinkle and Turner, {Stephen T.} and Paolo Manunta and Cristina Barlassina and Daniele Cusi and Nicola Glorioso",

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doi = "10.2217/pgs.14.119",

language = "English (US)",

volume = "15",

pages = "1643--1652",

journal = "Pharmacogenomics",

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TY - JOUR

T1 - Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan

T2 - The SOPHIA study

AU - Frau, Francesca

AU - Zaninello, Roberta

AU - Salvi, Erika

AU - Ortu, Maria Francesca

AU - Braga, Daniele

AU - Velayutham, Dinesh

AU - Argiolas, Giuseppe

AU - Fresu, Giovanni

AU - Troffa, Chiara

AU - Bulla, Emanuela

AU - Bulla, Patrizia

AU - Pitzoi, Silvia

AU - Piras, Daniela Antonella

AU - Glorioso, Valeria

AU - Chittani, Martina

AU - Bernini, Giampaolo

AU - Bardini, Michele

AU - Fallo, Francesco

AU - Malatino, Lorenzo

AU - Stancanelli, Benedetta

AU - Regolisti, Giuseppe

AU - Ferri, Claudio

AU - Desideri, Giovanbattista

AU - Scioli, Giuseppe Antonio

AU - Galletti, Ferruccio

AU - Sciacqua, Angela

AU - Perticone, Francesco

AU - Degli Esposti, Ezio

AU - Sturani, Alessandra

AU - Semplicini, Andrea

AU - Veglio, Franco

AU - Mulatero, Paolo

AU - Williams, Tracy A.

AU - Lanzani, Chiara

AU - Hiltunen, Timo P.

AU - Kontula, Kimmo

AU - Boerwinkle, Eric

AU - Turner, Stephen T.

AU - Manunta, Paolo

AU - Barlassina, Cristina

AU - Cusi, Daniele

AU - Glorioso, Nicola

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Background: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. Aim: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. Materials & methods: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. Results: We identified a peak of association in CAMK1D gene (rs10752271, effect size-5.5 ± 0.94 mmHg, p = 1.2 × 10-8). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. Conclusion: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension. Original submitted 7 May 2014; Revision submitted 29 July 201.

AB - Background: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. Aim: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. Materials & methods: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. Results: We identified a peak of association in CAMK1D gene (rs10752271, effect size-5.5 ± 0.94 mmHg, p = 1.2 × 10-8). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. Conclusion: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension. Original submitted 7 May 2014; Revision submitted 29 July 201.

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KW - genome-wide association analysis

KW - genomics

KW - hypertension

KW - losartan

KW - pharmacogenomics

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Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: The SOPHIA study

Abstract

Keywords

ASJC Scopus subject areas

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