1. Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study
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Lorenzo Malatino, Cristina Barlassina, Giuseppe Regolisti, Emanuela Bulla, Tracy Ann Williams, Franco Veglio, Alessandra Sturani, Martina Chittani, Erika Salvi, Daniele Cusi, Andrea Semplicini, Giovanni Fresu, Eric Boerwinkle, Patrizia Bulla, Timo P. Hiltunen, Giuseppe Argiolas, Francesca Frau, Paolo Manunta, Daniele Braga, Silvia Pitzoi, Paolo Mulatero, Giuseppe A. Scioli, Maria Francesca Ortu, Kimmo Kontula, Valeria Glorioso, Chiara Lanzani, Roberta Zaninello, Francesco Fallo, Daniela Antonella Piras, Ezio Degli Esposti, Benedetta Stancanelli, Angela Sciacqua, Ferruccio Galletti, Michele Bardini, Nicola Glorioso, Giovanbattista Desideri, Chiara Troffa, Dinesh Velayutham, Giampaolo Bernini, Francesco Perticone, Claudio Ferri, Stephen T. Turner, 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, Ferruccio, 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, and Glorioso, N. more...
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Male ,Angiotensin receptor ,losartan ,Blood Pressure ,Genome-wide association study ,030204 cardiovascular system & hematology ,Pharmacology ,Essential hypertension ,genomic ,chemistry.chemical_compound ,0302 clinical medicine ,Hydrochlorothiazide ,0303 health sciences ,angiotensin II receptor blockers ,Aldosterone ,genome-wide association analysi ,Medicine (all) ,Single Nucleotide ,Middle Aged ,3. Good health ,angiotensin II receptor blocker ,Losartan ,Molecular Medicine ,Female ,Arterial hypertension ,Genetic markers ,medicine.drug ,Adult ,hypertension ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,genomics ,Genetics ,medicine ,Humans ,Polymorphism ,angiotennsin II receptor ,pharmacogenomics ,030304 developmental biology ,business.industry ,medicine.disease ,genome-wide association analysis ,Angiotensin II Type 1 Receptor Blockers ,Calcium-Calmodulin-Dependent Protein Kinase Type 1 ,Hypertension ,Genome-Wide Association Study ,Blood pressure ,chemistry ,Pharmacogenomics ,business - 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 more...
- Published
- 2014
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