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CLINICAL RESEARCH: ATHEROSCLEROSIS

Effects of Ile164 Polymorphism of Beta₂-Adrenergic Receptor Gene on Coronary Artery Disease

Department of Clinical Medicine, Cardiovascular and Immunology Sciences, Federico II University School of Medicine, Naples, Italy

Manuscript received May 28, 2008; revised manuscript received July 7, 2008, accepted July 10, 2008.

^_* Reprint requests and correspondence: Prof. Federico Piscione, Department of Cardiology, Federico II University, Via S. Pansini, 5, 80131 Naples, Italy (Email: piscione{at}unina.it).

Objectives: This study investigated the relationship between beta₂-adrenergic receptor (B2AR) Ile164 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 (Ile164) 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 Ile164 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/Ile]). 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 Ile164 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 Ile164 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 Ile164 mutant is associated with a more aggressive CAD and adversely affects prognosis in patients undergoing PCI.

Key Words: beta₂-adrenergic receptor • single nucleotide polymorphism • vasodilation

Abbreviations and Acronyms   Ad = adenoviral   AMI = acute myocardial infarction   B2AR = beta2-adrenergic receptor   CAD = coronary artery disease   DNA = deoxyribonucleic acid   ERK = extracellular signal-related kinase   IBS = integrated backscatter   IMT = intima-media thickness   ISO = isoproterenol   MACE = major adverse cardiac event   PAD = peripheral artery disease   PCI = percutaneous coronary intervention   PCR = polymerase chain reaction   Rb = retinoblastoma protein   TIMI = Thrombolysis In Myocardial Infarction   VSMC = vascular smooth muscle cell   WT = wild type

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