title: Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hypertension & Related Disease Centre, AOU-University of Sassari, Sassari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Frau
authors.forename: Roberta
authors.initials: R
authors.lastname: Zaninello
authors.forename: Erika
authors.initials: E
authors.lastname: Salvi
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Ortu
authors.forename: Daniele
authors.initials: D
authors.lastname: Braga
authors.forename: Dinesh
authors.initials: D
authors.lastname: Velayutham
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Argiolas
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fresu
authors.forename: Chiara
authors.initials: C
authors.lastname: Troffa
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bulla
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bulla
authors.forename: Silvia
authors.initials: S
authors.lastname: Pitzoi
authors.forename: Daniela Antonella
authors.initials: DA
authors.lastname: Piras
authors.forename: Valeria
authors.initials: V
authors.lastname: Glorioso
authors.forename: Martina
authors.initials: M
authors.lastname: Chittani
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bernini
authors.forename: Michele
authors.initials: M
authors.lastname: Bardini
authors.forename: Francesco
authors.initials: F
authors.lastname: Fallo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Malatino
authors.forename: Benedetta
authors.initials: B
authors.lastname: Stancanelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Regolisti
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferri
authors.forename: Giovanbattista
authors.initials: G
authors.lastname: Desideri
authors.forename: Giuseppe Antonio
authors.initials: GA
authors.lastname: Scioli
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Galletti
authors.forename: Angela
authors.initials: A
authors.lastname: Sciacqua
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.forename: Ezio
authors.initials: E
authors.lastname: Degli Esposti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sturani
authors.forename: Andrea
authors.initials: A
authors.lastname: Semplicini
authors.forename: Franco
authors.initials: F
authors.lastname: Veglio
authors.forename: Paolo
authors.initials: P
authors.lastname: Mulatero
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Williams
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzani
authors.forename: Timo P
authors.initials: TP
authors.lastname: Hiltunen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Paolo
authors.initials: P
authors.lastname: Manunta
authors.forename: Cristina
authors.initials: C
authors.lastname: Barlassina
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
authors.forename: Nicola
authors.initials: N
authors.lastname: Glorioso
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D006852:Hydrochlorothiazide; C517601:CAMK1D protein, human; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D019808:Losartan
keywords: angiotensin II receptor blockers; genome-wide association analysis; genomics; hypertension; losartan; pharmacogenomics