Insertion/deletion polymorphism in α2-adrenergic receptor gene is a genetic risk factor for sudden cardiac death

BackgroundAdrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. A deletion variant of the human α2B-adrenoreseptor of glutamic acid residues has been associated with impaired receptor desensitization. This receptor variant could, therefore, be involved in cardiovascular diseases associated with enhanced vasoconstriction. Our aim was to study whether an insertion/deletion (I/D) polymorphism in the α2B-adrenoceptor gene is associated with the risk for sudden cardiac death.MethodsThis was a prospective population-based study investigating risk factors for cardiovascular diseases in middle-aged men from 42 to 60 years from eastern Finland. The study is based on 1,606 men with complete data on DNA observed for an average time of 17 years.ResultsIn this study population, 338 men (21%) had the D/D genotype, 467 (29%) had the I/I genotype, and 801 (50%) had a heterozygous genotype. There were 76 sudden cardiac deaths during follow-up (0.81 deaths/1,000 persons per year). In a Cox model adjusting for other coronary risk factors (age, systolic blood pressure, smoking, diabetes, serum low-density lipoprotein and high-density lipoprotein cholesterol, body mass index, and exercise-induced myocardial ischemia), men with the D/D or I/D genotype had 1.97 times (95% CI 1.08-3.59, P = .026) higher risk to experience sudden cardiac death (20 events for D/D genotype, 13 events for I/I genotype, and 43 events for I/D genotype) compared with men carrying the I/I genotype. In addition, the α2B-adrenoceptor D/D genotype was associated with the risk of coronary heart disease death and acute coronary events, after adjusting for risk factors.ConclusionsThe genetic polymorphism of the α2B-adrenoreceptor is genetic risk predictor for sudden cardiac death.