The impact of genetic polymorphisms of P2Y12, CYP3A5 and CYP2C19 on clopidogrel response variability in Iranian patients

Clopidogrel is an inhibitor of platelet ADP P2Y12 receptors and currently used for prevention of stent thrombosis. Despite certain clinical benefit using this drug in patients undergoing percutaneous coronary intervention (PCI), some patients do not attain adequate antiplatelet effects. In this study, we investigated the role of three genetic factors (P2Y12, CYP3A5, CYP2C19), demographic characteristics, and pathologic condition on clopidogrel response variability in Iranian patients after PCI. Patients who were candidate for elective PCI were enrolled in this study. All patients had received aspirin 80-325 mg daily for ≥ 1 week before PCI. Blood samples were taken from patients at baseline, 2 h after taking a 600-mg loading dose of clopidogrel, 24h and 30 days after PCI. Platelet aggregation was measured by turbidimetric aggregation assay with two different concentrations of ADP (5 and 20 μM). CYP2C19*2(rs4244285), CYP2C19*3(rs4986893), CYP3A5 (A6986G), and P2Y12 (T744C) genotypings were performed by PCR-RFLP. One hundred and twelve patients were included in this study. Maximum clopidogrel non-responsiveness (25.90%) occurred at 2 h after taking 600 mg of the loading dose of clopidogrel. Although there were no significant associations between clopidogrel responsiveness and polymorphisms of CYP2C19, CYP3A5, and P2Y12 (P > 0.05), subjects who were CYP3A5 genotype expressor had a greater inhibition of platelet aggregation. No significant associations were observed between environmental factors and clopidogrel responsiveness (P > 0.05). Our results showed that P2Y12, CYP3A5, and CYP2C19 polymorphisms along with non-genetic factors were not responsible for the interindividual variability in response to clopidogrel in Iranian population.