Both PON1 Q192R and CYP2C19*2 influence platelet response to clopidogrel and ischemic events in Chinese patients undergoing percutaneous coronary intervention

Clopidogrel nonresponsiveness increases the recurrence of cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). Previous studies found that genetic variants such as single nucleotide polymorphisms (SNPs) of CYP2C19 and PON1 may influence clopidogrel response, cause high platelet reactivity (HPR) and increase cardiovascular events. However, these studies were inconsistent and inconclusive, especially in the Eastern Asian population. In this study, we investigated the effects of genetic variants on clopidogrel response and clinical outcomes in Chinese patients undergoing PCI. A total of 336 acute coronary syndrome patients undergoing PCI were included, 53 (15.77%) of whom were categorized as HPR. Among the 10 SNPs studied (ABCB1, CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*17, CYP3A4, CYP3A5, ITGB3, P2Y12 and PON1 Q192R), the CYP2C19*4 and P2Y12 variants were not found in our population. The PON1 192Q and CYP2C19*2 alleles were significantly higher in the HPR group compared with the normal platelet reactivity (NPR) group (P=0.033 and 0.038, respectively), while the other SNPs were not significantly different between the two groups. Platelet aggregation of the PON1 192Q allele carriers was significantly higher than that of non-carriers both at baseline and 1 month after PCI (P=0.010 and 0.024, respectively); this was the case for CYP2C19*2 allele carriers, as well (P=0.005 and 0.003, respectively). The risk of major adverse cardiovascular event (MACE) increased with the presence of the PON1 192Q and CYP2C19*2 alleles during 6-month follow-up (P=0.012 and 0.003, respectively). In conclusion, both the PON1 Q192R and CYP2C19*2 variants are associated with HPR and an increased risk of ischemic events in Chinese patients undergoing PCI.