An insertion/deletion polymorphism in the alpha(2B)-adrenergic receptor gene is a novel genetic risk factor for acute coronary events

OBJECTIVES Our aim was to study whether an insertion/deletion (I/D) polymor phism in the alpha (2B)-adrenoceptor gene is associated with the risk for c ardiovascular diseases. BACKGROUND alpha (2)-adrenoceptors mediate contraction of vascular smooth m uscle and induce coronary vasoconstriction in humans. The alpha (2)-adrenoc eptor subtype B mediates vasoconstriction in mice. A variant of the human a lpha (2B)-adrenoceptor gene that encodes a D of three residues in an intrac ellular acidic motif has been shown to confer decreased receptor desensitiz ation. This receptor variant could, therefore, be involved in diseases asso ciated with enhanced vasoconstriction. METHODS This study was part of a prospective population-based study investi gating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve mon aged 46 to 64 years were followed for an average time of 4.5 years. RESULTS In this study population, 192 men (21%) had the D/D genotype; 256 ( 28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genot ype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 fo r I/D) compared with men carrying either of the other two genotypes. The al pha (2B)-adrenoceptor genotype was not associated with hypertension in this study population. CONCLUSIONS The D/D genotype of the alpha (2B)-adrenoceptor is a novel gene tic risk factor for acute coronary events, but not for hypertension. (J Am Coll Cardiol 2001;37:1516-22) (C) 2001 by the American College of Cardiolog y.