Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study.
Academic Article
Publication Date:
2014
Short description:
Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study / 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., Stancanelli, B., et al.. - In: PHARMACOGENOMICS. - ISSN 1462-2416. - 15:13(2014), pp. 1643-1652. [doi: 10.2217]
abstract:
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
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
Iris type:
1.1 Articolo in rivista
Keywords:
losartan; angiotensin I receptor blockers; hypertension
List of contributors:
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, Nicola Filippo
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