Abstract 18363: Platelet Aggregation in Stable Angina Patients Treated With Aspirin and Clopidogrel is Modulated by 6.3 / 6.7 Kb Polymorphism of the Platelet Alpha2a-Adrenergic Receptor
Purpose: Platelet α2A-adrenergic receptors (α2A-ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3 kb variant of α2A-AR gene has been associated with an increased epinephrine-mediated platelet aggregation in healthy volunteers. The aim of this study was to assess the potential influence of the 6.3/6.7 kb polymorphism of α2A-AR gene on residual platelet aggregation in stable angina patients taking dual anti-platelet therapy.
Methods: A total of 131 consecutive stable angina patients were screened for 6.3/6.7kb α2A-AR polymorphism. All patients were loaded with 600mg of clopidogrel and 500mg of aspirin at least 12 hours prior to platelet function testing. Whole blood aggregation was assessed in response to increasing doses of epinephrine (from 0.156 to 10 μmol/L), high sensitivity ADP (2 μmol/L + PGE1) and ADP (2 μmol/L) using the Multiplate® Platelet Function Analyzer.
Results: The single nucleotide polymorphism explored was in Hardy-Weinberg equilibrium. Genotype frequency was 62% for 6.7kb homozygote and 38% for 6.3kb carriers (only 1 homozygote 6.3kb). Factors known to influence platelet reactivity such as gender, age, body mass index, diabetes mellitus, hypertension, and smoking were equally distributed among the 2 groups. Platelet aggregation induced by epinephrine was significantly enhanced in 6.3kb carriers as compared with 6.7kb homozygotes (figure). Carriers of 6.3 kb variant showed also a significant enhancement of platelet aggregation induced by ADP (45±19U vs. 38±22U, p=0.04) and high sensitivity ADP (23±12U vs. 18±12U, p=0.04).
Conclusions: Genetic polymorphisms of the α2A adrenergic receptor may influence platelet reactivity in response to epinephrine and ADP in patients with stable angina despite loading with 600mg of clopidogrel and 500mg of aspirin. Therefore, carriers of this polymorphism may be at higher risk of cardiovascular events.
- © 2010 by American Heart Association, Inc.