Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study. (October 2014)

• Record Type: Journal Article
• Authors: Frau, Francesca; Zaninello, Roberta; Salvi, Erika; Ortu, Maria Francesca; Braga, Daniele; Velayutham, Dinesh; Argiolas, Giuseppe; Fresu, Giovanni; Troffa, Chiara; Bulla, Emanuela; Bulla, Patrizia; Pitzoi, Silvia; Piras, Daniela Antonella; Glorioso, Valeria; Chittani, Martina; Bernini, Giampaolo; Bardini, Michele; Fallo, Francesco; Malatino, Lorenzo; Stancanelli, Benedetta; Regolisti, Giuseppe; Ferri, Claudio; Desideri, Giovanbattista; Scioli, Giuseppe Antonio; Galletti, Ferruccio; Sciacqua, Angela; Perticone, Francesco; Degli Esposti, Ezio; Sturani, Alessandra; Semplicini, Andrea; Veglio, Franco; Mulatero, Paolo; Williams, Tracy A; Lanzani, Chiara; Hiltunen, Timo P; Kontula, Kimmo; Boerwinkle, Eric; Turner, Stephen T; Manunta, Paolo; Barlassina, Cristina; Cusi, Daniele; Glorioso, Nicola;
• Is Part Of: Pharmacogenomics. Volume 15:Number 13(2014)
• Page Start: 1643
• Page End: 1652
• Publication Date: 2014-10
• Subjects: angiotensin II receptor blockers -- genome-wide association analysis -- genomics -- hypertension -- losartan -- pharmacogenomics; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.14.119
• Languages: English
• ISSNs: 1462-2416

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 2014