Abstract 5017: An Insertion/Deletion Polyporphism in α 2 -Adrenergic Receptor Gene is a Novel Genetic Risk Factors Sudden Cardiac Death

Abstract

α 2B -adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. A variant of the human α 2B -adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased 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 α 2B -adrenoceptor gene is associated with the risk for sudden cardiac death. This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. The study is based on 1606 men 42 to 60 years of age followed for an average time of 17 years. In 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. In a Cox model adjusting for other coronary risk factors (age, systolic blood pressure, smoking, diabetes, serum LDL and HDL cholesterol, body mass index and exercise-induced myocardial ischemia), men with the D/D or I/D genotype had 1.95 time (95% confidence interval, 1.07 to 3.55, P = 0.029) 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. The α 2B -adrenoceptor genotype was associated with coronary heart disease death but not with hypertension. The D/D and I/D genotypes of the α 2B -adrenoceptor are novel genetic risk predictors for sudden cardiac death.