title: RyR2 Common Gene Variant G1886S and the Risk of Ventricular Arrhythmias in ICD Patients with Heart Failure.
abstract: BACKGROUND
  Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel destabilization and enhanced intracellular Ca(2+) oscillation, thus promoting cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is associated with aborted sudden cardiac death or ICD therapy for ventricular tachycardia (VT)/fibrillation (VF) in heart failure (HF) patients implanted with a cardioverter defibrillator (ICD).
  
  
  RESULTS
  A total of 183 HF patients with primary or secondary prevention ICD were divided in 2 groups. A VT/VF group was composed of secondary prevention patients and primary prevention patients with appropriate ICD intervention for VT/VF. An ICD control group was composed of primary prevention patients free from any appropriate ICD intervention after 43 ± 25 months follow-up. Study subjects were genotyped with respect to the rs3766871 RyR2 gene variant. Hazard ratios (HRs) were derived from Cox proportional-hazards regression analysis. In all, 56 patients constituted the VT/VF group and 127 patients the ICD control group. Male sex (HR: 3.02; 95% CI: 0.99-9.18; P = 0.05), atrial fibrillation (AF; HR: 2.33; 95% CI: 0.89-6.10; P = 0.08), and underuse of β-blockers (HR: 2.08; 95% CI: 0.84-5.15; P = 0.11) were associated with the VT/VF phenotype. Prevalence of the rs3766871 minor allele was 2.8% in ICD control patients and 8.0% in the VT/VF group (P = 0.02). After adjustment for age, sex, AF, and use of β-blockers, the rs3766871 minor allele was associated with increased risk of VT/VF (HR: 3.49; 95% CI: 1.14-10.62; P = 0.02).
  
  
  CONCLUSIONS
  Our study identifies a significant role of RyR2 rs3766871 minor allele for increased susceptibility to VT/VF in a population of ICD patients with HF.
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Pietro
authors.initials: P
authors.lastname: Francia
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Carmen
authors.initials: C
authors.lastname: Adduci
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Semprini
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Stanzione
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Andrea
authors.initials: A
authors.lastname: Serdoz
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Massimo
authors.initials: M
authors.lastname: Caprinozzi
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Daria
authors.initials: D
authors.lastname: Santini
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cotugno
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Francesca
authors.initials: F
authors.lastname: Palano
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Musumeci
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.|I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.affiliation: Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.|I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D016757:Death, Sudden, Cardiac / Q000473:pathology; D017147:Defibrillators, Implantable; D005260:Female; D060005:Genotyping Techniques; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000235:genetics*; D014693:Ventricular Fibrillation / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel
keywords: RyR2; calcium handling proteins; gene variants; heart failure; implantable cardioverter defibrillator; sudden death