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

• Published in: Pharmacogenomics Vol. 15; no. 13; pp. 1643 - 1652
• Main 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
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.10.2014
• Subjects: Adult; angiotensin II receptor blockers; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Blood Pressure - drug effects; Calcium-Calmodulin-Dependent Protein Kinase Type 1 - genetics; Drug metabolism; Drug therapy; Female; Genetic aspects; Genetic polymorphisms; genome-wide association analysis; Genome-Wide Association Study; genomics; Humans; Hydrochlorothiazide - therapeutic use; Hypertension; Hypertension - drug therapy; Hypertension - genetics; Hypertension - physiopathology; Identification and classification; Losartan; Losartan - pharmacology; Losartan - therapeutic use; Male; Middle Aged; Patient outcomes; pharmacogenomics; Polymorphism, Single Nucleotide; genomics; pharmacogenomics; losartan; hypertension; angiotensin II receptor blockers; genome-wide association analysis
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs.14.119

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. 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. 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. We identified a peak of association in gene (rs10752271, effect size -5.5 ± 0.94 mmHg, p = 1.2 × 10 ). 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 the GENRES cohort. Using a genome-wide approach, we identified the gene as a novel locus associated with blood pressure response to losartan. gene characterization may represent a useful tool to personalize the treatment of essential hypertension. Original submitted 7 May 2014; Revision submitted 29 July 2014