Correlation Of MDR1, CYP2C19and CYP3A5Gene Polymorphisms With The Effect Of Clopidogrel

The aim of this study was to evaluate the relative impact of the MDR1and cytochrome P4502C19(CYP2C19) and cytochrome P4503A5(CYP3A5) polymorphism on antiplatelet effects of clopidogrel in patientswith coronary artery disease undergoing percutaneous coronaryintervention (PCI).137patients were considered in our study. The gene chip was used tomeasure the genotype of CYP2C19including CYP2C19*2and*3twomutational sites. And gene sequencing was used to measure the genotypeof MDR1and CYP3A5*3by the PCR products of them. TEG was used tomeasure the ADP-inhibition which indicated the platelet function ofpatients after taking clopidogrel. Then the difference of ADP inhibitionbetween different groups of genotypes were compared.Genotype analysis revealed the following frequency among the137patients:67(48.91%) had the CYP2C19*1/*1allele,50(36.50%) had the*1/*2allele,8(5.84%) had the*1/*3allele,8(5.84%) had the*2/*2allele,3(2.19%) had the*2/*3allele, and1(0.73%) had the*3/*3allele;48(35.04%) had the MDR1CC allele,68(49.64%)had the CT allele, and21(15.33%) had the TT allele;13(9.49%) had the CYP3A5*1/*1allele,49(35.77%) had the*1/*3allele, and75(54.74%) had the*3/*3allele. themutation allele frequency of CYP2C19*2was25.18%, CYP2C19*3was4.74%, MDR1C3435T was40.14%, and the mutation alle frequency ofCYP3A5*3was72.63%.The ADP-inhibition in patients with extensive metabolism （EM）ofCYP2C19was (41.99±26.86)%, and the poor metabolism(PM) was (33.67 ±20.53)%. There was significant difference between the two metabolizers(P=0.019).The ADP-inhibition in patients with EM of MDR1was40.25±25.79%, and the PM was (36.38±23.19)%. There was no significantdifference between the two metabolizers (P=0.65).The ADP-inhibition in patients with EM of CYP3A5was (37.93±24.30)%, and the PM was (37.57±24.11)%. There was no significantdifference between the two metabolizers (P=0.83).There was significant difference in MDR1and CYP2C19genecombination on ADP inhibition rate. The ADP inhibition rate in patientscarrying poor metabolism of CYP2C19and MDR1was lower than that inextensive metabolism groups (P<0.05). There was no significant differencein CYP3A5and CYP2C19gene combination on ADP inhibition rate.The MDR1and CYP2C19gene polymorphisms influence inanticoagulant effect of clopidogrel in patients with coronary artery diseaseunderwent percutaneous coronary intervention(PCI), but the CYP3A5dosenot. The anticoagulant effect in patients carrying poor metabolism ofCYP2C19is lower than that of extensive metabolism. The poor metabolismof CYP2C19carriers, especially poor metabolism of MDR1carriers, needhigher dose of clopidogrel than extensive metabolism of CYP2C19carriers,in order to achieve anticoagulant effect well. Evaluating the CYP2C19andMDR1polymorphism of the recipients may be helpful in personalized usedof clopidogrel.