Association between Beta sub(1)-Adrenergic Receptor Polymorphism and Risk of ICD Shock in Heart Failure Patients

Background Sympathetic activation in heart failure patients favors the development of ventricular arrhythmias, thus leading to an increased risk of sudden cardiac death. beta sub(1)- and beta sub(2)-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 beta sub(1)- and beta sub(2)-adrenergic receptor polymorphisms are associated with risk of ICD shocks, as evidenced in ICD memory. Methods 311 patients with systolic heart failure were enrolled, and number and timing of shocks in ICD memory were recorded. Four selected polymorphisms were determined: beta sub(1)-adrenergic receptor polymorphisms Ser super(49)Gly and Arg super(389)Gly and beta sub(2)-adrenergic receptor polymorphisms Arg super(16)Gly and Gln super(27)Glu. Results Only Ser super(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). Conclusions Data from our study suggest that the beta adrenoreceptor Gly 49 allele of the beta sub(1)-adrenergic receptor Ser super(49)Gly polymorphisms may increase the risk of ICD shock in patients with heart failure, independent of beta-blocker dosage.