P2Y12 receptor gene polymorphism and antiplatelet effect of clopidogrel in patients with coronary artery disease after coronary stenting

Abstract

Platelets have a central role in the pathophysiology of thrombosis. Adenosine diphosphate (ADP) plays a pivotal role as an agonist of platelet activation. Genetic polymorphisms of the P2Y12 ADP receptor might influence the activation of this receptor by ADP or the response of patients to platelet inhibitors. The present study was conducted on a total number of 80 participants, 40 patients were diagnosed with acute coronary syndrome and 40 sex and aged-matched healthy volunteers were included as controls. Platelet aggregation was assessed (before and 1 week after clopidogrel administration) and genotyping of the T744C genetic polymorphism of P2Y12 receptor gene was carried out using the restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method. Platelet aggregation of the patients had a range of 54-183% before clopidogrel administration and had a range of 4-113% after its administration. Genotyping of the candidate gene revealed that 72.5% of the patients had a wild allele (TT), whereas 27.5% had a C allele (heterozygous CT, homozygous CC). On the contrary, 97.5% of controls had a wild allele (TT), whereas 2.5% had a C allele (heterozygous CT, homozygous CC). Our study elicited an association between the T744C polymorphism of the P2Y12 ADP receptor gene and platelet reactivity. Carrying the C allele at this position is associated with an increased platelet activation response to ADP.

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

“…In a study on Egyptian population, it was found that the i744T>C polymorphism is associated with an increased platelet activation response to ADP (Zoheir et al 2013). A study done on 112 Iranian subjects concluded that the P2Y12 polymorphisms may be implicated in clopidogrel response variability (Azarpira et al 2011).…”

Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke

“…The P2RY12 gene encodes the P2Y12 receptor protein, which is the pharmacological target of clopidogrel. Genetic polymorphisms of the P2Y12 ADP receptor might alter the receptor activation induced by ADP or the response to platelet inhibitors in patients [36] . Goran et al reported that P2RY12 (rs2046934) was consistently associated with a higher platelet reactivity in patients on clopidogrel in the ADP-induced LTA and the VerifyNow P2Y12 assay; this may provide protection against atherothrombotic events [16] .…”

Cardiac purinergic signalling in health and disease

“…Clinical trials with clopidogrel and ticlopidine in patients with CAD have shown significant benefit compared with aspirin. An association between the T744C polymorphism of the P2Y12R gene and the antiplatelet effect of clopidogrel was found in patients with CAD after coronary stenting [767]. ADP receptor antagonist discontinuation prior to coronary artery bypass surgery has been recommended [768,769].…”