GLU-27 variant of β2-adrenergic receptor polymorphisms is an independent risk factor for coronary atherosclerotic disease

Objective: Arg16Gly and Gln27Glu polymorphism of β2-adrenergic receptors (β2AR) have been associated with several risk factors for coronary atherosclerotic disease (CAD). Nevertheless, conflicting data have been reported concerning their influence on CAD and cardiovascular clinical events. Aim: To investigate whether (a) β2AR polymorphisms are associated with CAD; and (b) the potential impact, if any, of these polymorphisms on cardiovascular clinical events in patients presenting with angina-like pain or silent ischemia. Methods and results: We screened 786 consecutive patients referred to cardiac catheterization because of angina-like pain or silent ischemia for Arg16Gly, Gln27Glu, Thr164Ile β2AR polymorphisms. Patients were divided in 2 groups according to the presence or absence of CAD at the angiography. Hundred subjects from blood donor center served as controls. Clinical endpoints were evaluated at baseline and up to 6 years follow-up. Glu-27 homozygous genotype and Glu-27 allele (Glu-27, allele frequency: 47% CAD versus 39% NO CAD, p < 0.05) were more frequent in patients with CAD. At multivariate analysis, patients carrying Glu-27 allele showed a significantly higher risk of developing CAD (OR: 1.78, 95% CI: 1.21-2.63, p = 0.004). At clinical follow-up, a higher incidence of coronary revascularization was noted in Glu-27 homozygotes as compared with Gln-27 homozygote patients. Conclusions: In patients at high risk for CAD and/or angina-like pain, Glu-27 allele of β2 adrenergic receptor polymorphism is an independent risk factor for CAD and appears to be associated with higher incidence of myocardial revascularization. © 2006 Elsevier Ireland Ltd. All rights reserved.