β 2 -Adrenergic Receptor Polymorphisms and Sudden Cardiac Death

Abstract

Sudden cardiac death (SCD) is defined as an unexpected death from a cardiac cause generally within 1 hour of the onset of symptoms. The great majority of SCD cases are due to ventricular fibrillation and subsequent hemodynamic collapse. Eighty percent of SCD is attributable to ischemic heart disease, with much of the remainder caused by cardiomyopathies/heart failure and intrinsic conduction system abnormalities.1 These predisposing conditions place patients at risk for SCD, and a trigger for the fatal arrhythmias may come from an imbalance of the parasympathetic and sympathetic nervous systems,2–5 the latter being mediated by cardiac β1- and β2-adrenergic receptors (β1AR, β2AR). Indeed, treatment with β-blockers of patients with heart failure and those who have suffered a myocardial infarction significantly reduces ventricular tachyarrhythmias and SCD. Typically, the pathophysiology of SCD is considered in terms of the underlying disease. However, there is evidence for genetic variability of the β1AR and β2AR genes that has functional consequence in transfected cells, endogenously expressing cells, and transgenic mice.6,7 Familial clustering of certain pathological arrhythmias and the unexplained variability in susceptibility among unrelated individuals to fatal arrhythmias raise the possibility of common polymorphisms such as those of the β1AR or β2AR being genetic risk factors for SCD. Article p 1842 In this issue of Circulation , Sotoodehnia et al8 examined polymorphisms of the β2AR and potential associations with SCD. The study used individuals in the Cardiovascular Health Study (CHS), amounting to 4441 European Americans and 808 African Americans, with SCD occurring in 156 and 39 cases, respectively. In this population, homozygosity for Gln27 was associated with a hazard ratio (HR) of 1.56 (95% confidence interval [CI], 1.17 to 2.09) for SCD compared with …