C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention
2015; Elsevier BV; Volume: 136; Issue: 5 Linguagem: Inglês
10.1016/j.thromres.2015.08.025
ISSN1879-2472
AutoresBeatriz Calderón‐Cruz, Karen Rodríguez-Galván, Luis Antonio Manzo-Francisco, Gilberto Vargas‐Alarcón, José Manuel Fragoso, Marco Antonio Peña‐Duque, Carlos Alberto Reyes-Gómez, Marco Antonio Martínez‐Ríos, Aurora de la Peña-Dı́az,
Tópico(s)Inflammatory mediators and NSAID effects
ResumoBackground Clopidogrel is a pro-drug and its intestinal absorption is limited by the P-glycoprotein encoded by the ABCB1 gene. It is metabolized hepatically by cytochrome P450 enzymes encoded by CYP genes to produce an active metabolite that antagonizes the P2Y12 platelet receptor. Some patients exhibit poor clopidogrel responsiveness due to polymorphisms, resulting in thrombotic events. The aim of this study was to determine the relationship between poor clopidogrel responsiveness and the ABCB1, CYP and P2RY12 gene polymorphisms among patients undergoing percutaneous coronary intervention (PCI). Methods and results Two hundred seventy-six patients who underwent PCI were included in this study. Clopidogrel responsiveness was determined via optical aggregometry in platelet-rich plasma using 10 μM ADP. Patients exhibiting a platelet aggregation response higher than 70% were classified as poor responders. The genetic polymorphisms were analyzed via real-time PCR. Poor responsiveness to clopidogrel was noted in 22.1% of the patients. The TT genotype of the C3435T polymorphism of the ABCB1 gene and omeprazole usage were each associated with poor clopidogrel responsiveness (Exp (β) 2.73, p = 0.009 and Exp (β) 3.86, p = 0.04, respectively). Conclusion Poor clopidogrel responsiveness is associated with the TT genotype of the C3435T polymorphism of the ABCB1 gene.
Referência(s)