Effects of IIe164 Polymorphism of Beta2-Adrenergic Receptor Gene on Coronary Artery Disease

Objectives This study investigated the relationship between beta(2)-adrenergic receptor (B2AR) IIe164 polymorphism and coronary artery disease (CAD). Background B2ARs are crucial to the regulation of vascular tone, and neoangiogenesis is impaired in the presence of isoleucine at position 164 (IIe164) B2AR gene polymorphism. No data deal with the role of the variants at position 164 of the B2AR gene in the setting of CAD. Methods The study population consisted of 330 patients undergoing percutaneous coronary intervention (PCI). Results The IIe164 polymorphism frequency was higher in CAD (12.1% vs. 3%, p = 0.008) with respect to the control population. We divided our population into 2 groups: group 1 (290 patients, threonine/threonine genotype at position 164 [164Thr/Thr]) and group 2 (40 patients, threonine/isoleucine genotype at position 164 [164Thr/ IIe]). Patients of group 2 presented an earlier onset of CAD (56.7 +/- 7.8 vs. 59.5 +/- 10, p = 0.04) and a higher incidence of multivessel disease (25.4% vs. 41%, p = 0.044). At follow-up, group 2 showed a higher incidence of new acute myocardial infarction (17.5% vs. 4.5%, p = 0.001), new PCI (37.5% vs. 13.1%, p < 0.0001), and cardiac death (10% vs. 3.1%, p = 0.036). Cox regression analysis identified IIe164 as an independent predictor of cardiac death (odds ratio [OR]: 3.731, 95% confidence interval [CI]: 1.004 to 13.867, p = 0.049) and an overall major adverse cardiac event (OR: 4.100, 95% CI: 1.945 to 8.640, p = 0.0001). A replication study was done on a population of 150 patients with peripheral artery disease. The presence of the IIe164 allele was associated with a higher incidence of acute myocardial infarction (54.5% vs. 25.2%, p = 0.035) or combined events (acute myocardial infarction, PCI, or coronary artery bypass graft) (63.6% vs. 30.9%, p = 0.027). Conclusions Our study suggests that the B2AR IIe164 mutant is associated with a more aggressive CAD and adversely affects prognosis in patients undergoing PCI. (J Am Coll Cardiol 2008; 52: 1381-8) (C) 2008 by the American College of Cardiology Foundation