Genetic polymorphisms of the platelet receptors P2Y₁₂, P2Y₁ and GP IIIa and response to aspirin and clopidogrel

Introduction: There is wide variability in the responses of individual patients to aspirin and clopidogrel. Polymorphisms of several platelet receptors have been related to increased platelet aggregation. We therefore aimed to evaluate whether these polymorphisms are related to altered response to aspirin or clopidogrel. Materials and methods: Patients (n = 120) undergoing percutaneous coronary intervention who received aspirin for ≥ 1 week but not clopidogrel were included. Blood samples were drawn at baseline and 20-24 h after a 300-mg clopidogrel dose. Aspirin insensitivity was defined as 5 μM ADP-induced aggregation ≥ 70% and 0.5 mg/mL arachidonic acid-induced aggregation ≥ 20%. Clopidogrel insensitivity was defined as baseline minus post-treatment aggregation ≤ 10% in response to 5 and 20 μM ADP. PlA polymorphism of glycoprotein IIIa, T744C polymorphism of the P2Y₁₂ gene and the 1622A > G polymorphism of the P2Y₁ gene were genotyped by polymerase chain reaction. Results: There were no differences in polymorphism frequencies between drug-insensitive vs. drug-sensitive patients. There were also no significant differences in response to aspirin (assessed by arachidonic acid-induced aggregation) or to clopidogrel (assessed by ADP-induced aggregation or activation markers) when patients were grouped according to genotype. The only trend observed was lower reduction in PAC-1 binding following clopidogrel in PlA₂ carriers (P = 0.065). Conclusions: We did not find an association between polymorphisms in the platelet receptors GP IIIa, P2Y₁₂ or P2Y₁ and response to aspirin or clopidogrel in cardiac patients. These findings suggest that the variability in response to anti-platelet drugs is multi-factorial and is not caused only by single gene mutations.