The impact of CYP3A5*1/*3, PIA1/A2 and T744C polymorphisms on clopidogrel and acetylsalicylic acid response variability in Mexican population

Abstract

Introduction: Clopidogrel is recommended in addition to aspirin to prevent atherothrombotic events in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, an interindividual variability in platelet inhibition response to clopidogrel has been demonstrated, and is associated with recurrent cardiovascular events. Multiple mechanisms have been associated with no response including genetics factors.

Materials and methods: The present study enrolled 60 patients with ACS undergoing emergent PCI. Platelet aggregation to adenosine diphosphate and arachidonic acid was assessed by turbidimetric method at 24 hours after dual administration of 300 mg of clopidogrel and 300 mg of acetylsalicylic acid loading dose. Clopidogrel or acetylsalicylic acid resistance was defined by persistence of Platelet Reactivity (PR=ADP-Ag >70% or PR=Arachidonic Acid-Ag>20%) respectively. The CYP3A51*/5*, PIA1/A2, and T744C polymorphisms were determined in all participants by PCR-RFLP.

Results: The allelic frequencies were: CYP3A5*3 (71.65%), PIA2 (10.8%), and 744 C (15.0%). We founded high percent of clopidogrel resistance (60.0%), compared with 8.3% of acetylsalicylic acid in those patients. The genotype frequencies of those polymorphisms were similar between responders and non responders defined by PR. There was a high percent of coronary adverse events.

Conclusions: We identified a high percent of clopidogrel resistance in Mexican patients with ACS undergoing PCI. However, a normal platelet response to acetylsalicylic acid was observed in most of them. There was no association between CYP3A5*1/*3, PIA1/A2, and T744C polymorphisms and clopidogrel resistance. More studies are needed to determine the possible interaction between genetics factors, platelet response to clopidogrel and cardiovascular adverse events.