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

Research output: Contribution to journalArticle

19 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 languageEnglish (US)
Pages (from-to)1643-1652
Number of pages10
JournalPharmacogenomics
Volume15
Issue number13
DOIs
StatePublished - 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