Association Between PON1Gene Polymorphisms And Clopidogrel Resistance

ObjectiveClopidogrel requires bioactivation in vivo to convert the pro-drug into itsactive metabolite to show its antiplatelet effects. The variability in the clinicalresponse to clopidogrel treatment has been attributed to genetic factors, butthe specific genes and mechanisms underlying clopidogrel bioactivationremain unclear. Recent studies report that Paraoxonase-1(PON1) as a keyenzyme play vital part in clopidogrel bioactivation. The aim of our study was toassess whether PON1gene polymorphisms are correlation with clopidogrelresistance (CR) in patients receiving clopidogrel after percutaneous coronaryintervention (PCI).MethodsA total of851patients undergoing PCI were enrolled in this study. Thosepatients involved were treated with clopidogrel (600mg or300mg) andaspirin(300mg). According to clopidogrel response which was assessed bypost-treatment20μmol/L ADP-induced residual platelet agglutination (RPA),RPA≥70%was defined as clopidogrel resistance (CR). Genomic DNA wasextracted from white cells by DNA extraction kit. Five SNPs were choosen fromthe hottest foreign studies. The methods of polymerase chain reaction (PCR)and direct sequencing were used to determined the genotypes of PON1gene.In addition, activity level of PON1towards phenylacetate was measured byspectro-photometrically at270nm. ResultsFive tagSNPs were selected in our study, which are rs662、rs854560、rs705379、rs705381、rs854572. The genotype frequencies of all studied SNPswere well to the Hardy-Weinberg equilibrium in both CR group and NCR group.Between the two groups, the five SNPs have the similar genotype and allelefrequency, no significant difference were observed between the two groups(P>0.05). The serum PON1activity was lower in CR group as compared tothe NCR group, but not statistically significant (P=0.554). In the two groups,we did not observed any significant difference between PON1genepolymorphisms, activity and CR.ConclusionsThis study demonstrates that neither PON1gene polymorphisms norPON1activity are associated with CR in patients receiving clopidogrel afterPCI.