title: Association between Beta1 -Adrenergic Receptor Polymorphism and Risk of ICD Shock in Heart Failure Patients.
abstract: Sympathetic activation in heart failure patients favors the development of ventricular arrhythmias, thus leading to an increased risk of sudden cardiac death. β1 - and β2 -adrenergic receptor polymorphisms have been linked to the risk of sudden death. Implantable cardioverter-defibrillators (ICD) are implanted in a large percentage of heart failure patients, and beyond preventing sudden cardiac death they provide a continuous monitoring of major ventricular arrhythmias and of their own interventions. We investigated whether functionally relevant β1 - and β2 -adrenergic receptor polymorphisms are associated with risk of ICD shocks, as evidenced in ICD memory.
  
  
  
  311 patients with systolic heart failure were enrolled, and number and timing of shocks in ICD memory were recorded. Four selected polymorphisms were determined: β1 -adrenergic receptor polymorphisms Ser(49) Gly and Arg(389) Gly and β2 -adrenergic receptor polymorphisms Arg(16) Gly and Gln(27) Glu.
  
  
  
  Only Ser(49) Gly was significantly correlated with time free from ICD shocks, both considering time to the first event in a Cox model (hazard ratio 2.117), and modeling repeated events with the Andersen-Gill method (hazard ratio 2.088). Gly allele carriers had a higher probability of ICD shock. The relationship remained significant even after adjusting for ejection fraction and beta-blocker dosage (hazard ratio 1.910).
  
  
  
  Data from our study suggest that the β adrenoreceptor Gly 49 allele of the β1 -adrenergic receptor Ser(49) Gly polymorphisms may increase the risk of ICD shock in patients with heart failure, independent of beta-blocker dosage.
authors.affiliation: Department of Medicine, Cardiology Division, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Zanolla
authors.affiliation: Department of Medicine, Cardiology Division, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Guarise
authors.affiliation: Department of Medicine, Cardiology Division, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tomasi
authors.affiliation: Department of Medicine, Cardiology Division, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Vassanelli
authors.affiliation: Struttura Complessa di Cardiologia, Dipartimento Cardio-Toraco, Vascolare Azienda Ospedaliera "Carlo Poma,", Mantova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cicorella
authors.affiliation: Struttura Complessa di Cardiologia, Dipartimento Cardio-Toraco, Vascolare Azienda Ospedaliera "Carlo Poma,", Mantova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zanini
authors.affiliation: Department Medical Sciences, University of Torino, Torino, Italy.|Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Guarrera
authors.affiliation: Department Medical Sciences, University of Torino, Torino, Italy.|Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fiorito
authors.affiliation: Department Medical Sciences, University of Torino, Torino, Italy.|Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
mesh_terms: D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors
chemical_list: D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2
keywords: congestive heart failure; defibrillation-ICD