Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study-Reference-Cited by-同舟云学术

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

Published:2014-09 Issue:13 Volume:15 Page:1643-1652
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Frau Francesca¹²³,Zaninello Roberta¹,Salvi Erika²³,Ortu Maria Francesca¹,Braga Daniele²³,Velayutham Dinesh²³,Argiolas Giuseppe¹,Fresu Giovanni¹,Troffa Chiara¹,Bulla Emanuela⁴,Bulla Patrizia¹,Pitzoi Silvia¹,Piras Daniela Antonella¹,Glorioso Valeria¹,Chittani Martina²³,Bernini Giampaolo⁵,Bardini Michele⁵,Fallo Francesco⁶,Malatino Lorenzo⁷,Stancanelli Benedetta⁷,Regolisti Giuseppe⁸,Ferri Claudio⁹,Desideri Giovanbattista⁹,Scioli Giuseppe Antonio¹⁰,Galletti Ferruccio¹¹,Sciacqua Angela¹²,Perticone Francesco¹²,Degli Esposti Ezio¹³,Sturani Alessandra¹⁴,Semplicini Andrea¹⁵,Veglio Franco¹⁶,Mulatero Paolo¹⁶,Williams Tracy A¹⁶,Lanzani Chiara¹⁷,Hiltunen Timo P¹⁸,Kontula Kimmo¹⁸,Boerwinkle Eric¹⁹,Turner Stephen T²⁰,Manunta Paolo¹⁷,Barlassina Cristina²³,Cusi Daniele²³,Glorioso Nicola¹

Affiliation:

1. Hypertension & Related Disease Centre, AOU-University of Sassari, Sassari, Italy

2. Department of Health Sciences, University of Milan at San Paolo Hospital, Milan, Italy

3. Filarete Foundation, Genomics & Bioinformatics Unit, Milan, Italy

4. Hypertension Center, ASL Sassari, Sassari, Italy

5. Department of Internal Medicine, University of Pisa, Pisa, Italy

6. Department of Medicine, University of Padova, Padova, Italy

7. Department of Medicine & Hypertension Center, University of Catania at Cannizzaro Hospital, Catania, Italy

8. Department of Clinical Science, University of Parma, Parma, Italy

9. Department of Internal Medicine & Public Health, University of L'Aquila, L'Aquila, Italy

10. ASREM “F. Veneziale” Hospital, Isernia, Italy

11. Department of Clinical Medicine & Surgery, “Federico II University” Medical School, Napoli, Italy

12. Department of Medical & Surgical Sciences, Cardiovascular Disease Unit, University of Catanzaro “Magna Graecia”, Catanzaro, Italy

13. CliCon Health, Economics & Outcomes Research, Ravenna, Italy

14. Nephrology & Dialysis Unit, S.M. delle Croci Hospital, Ravenna, Italy

15. UOC Internal Medicine 1, SS. Giovanni e Paolo Hospital, Campo SS. Giovanni e Paolo, Venice, Italy

16. Division of Internal Medicine & Hypertension Center, Department of Medical Sciences, AO Città Salute e Scienza, University of Torino, Torino, Italy

17. Università Vita Salute San Raffaele, Nephrology, Dialysis & Hypertension Unit, San Raffaele Scientific Institute, Milan, Italy

18. Department of Medicine, University of Helsinki & Helsinki University Central Hospital, Helsinki, Finland

19. Human Genetics & Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA

20. Division of Nephrology & Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA

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

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs.14.119

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