CYP2C19*2 and other genetic variants affecting platelet response to clopidogrel in patients undergoing percutaneous coronary intervention |
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Authors: | Kassimis George Davlouros Periklis Xanthopoulou Ioanna Stavrou Eleana F Athanassiadou Aglaia Alexopoulos Dimitrios |
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Institution: | a Cardiology Department, University Hospital of Patras, Greeceb Laboratory of General Biology, School of Medicine, University of Patras, Greece |
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Abstract: | IntroductionInformation regarding any possible additional effect of genetic variants other than CYP2C19*2 on platelet reactivity in patients undergoing percutaneous coronary intervention (PCI), while on dual antiplatelet therapy, is sparse.Materials and MethodsGenotyping for CYP2C19*2, CYP2C19*17, CYP2C9*3, CYP2B6*5, ABCB1 and P2RY12 (c.-217 + 2739 T > C) variants was performed in 146 consecutive PCI patients receiving clopidogrel. Platelet reactivity was assessed by the Verify Now P2Y12 point-of-care assay and high on-treatment platelet reactivity (HTPR) was defined as a Platelet Reactivity Unit (PRU) ≥ 235.ResultsWe identified 65(44.5%) patients with HTPR and 38(26%) carriers of at least one CYP2C19*2 allele, which had higher platelet reactivity compared to non-carriers least square (LS) mean difference 44.5, 95%CI 15.8-77.3, p = 0.003]. In the entire study population, the presence of at least one CYP2C19*2 or P2RY12 allelic variant was independently associated with HTPR (OR = 3.02, 95%CI 1.16-7.86, p = 0.023 and OR = 3.11, 95%CI 1.03-9.39, p = 0.05 respectively). In CYP2C19*2 non-carriers, carriers of at least one CYP2B6*5 allelic variant had higher platelet reactivity compared to the remainders (LS mean difference 35.6, 95%CI 3.7-67.6, p = 0.03) and the presence of at least one CYP2B6*5 or P2RY12 allelic variant was independently associated with HTPR (OR = 3.26, 95%CI 1.08-9.86, p = 0.04 and OR = 4.27, 95%CI 1.11-16.4, p = 0.04 respectively).ConclusionsApart from the CYP2C19*2, other genetic variants involved in clopidogrel metabolism and action like CYP2B6*5 and P2RY12 seem to have an important association with HTPR. |
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Keywords: | Clopidogrel Percutaneous coronary intervention Platelet reactivity CYP2C19 CYP2B6*5 P2RY12 |
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