Relation of cytochrome P450 2C19 gene 681G>A single nucleotide polynmrphism to clopidogrel resist

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Objectives Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450(CYP) isoenzymes to inhibit platelet aggregation.Individualvariability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness.In this study,we sought to determine the association between the single nucleotide polymorphism of CYP 2C19 681G>A and the occurrence of clopidogrel resistance(CR) in Chinese.Methods The study enrolled 614 hospitalized patients who underwentsuccessful percutaneouscoronary intervention with drug-eluting stents were received the treatmentwith dual antiplatelet regimen(aspirin plus clopidogrel).All patients received loading doses of 600 mg clopidogrel and 300 mg aspirin.20μmol/L ADP-induced platelet aggregation ratio(PAR ) was assessed 24 h after clopi- dogrel administration.The maximum residual PAR≥70%was defined as CR.Genomic DNA was extracted from whole blood samples according to standard protocols,the single nucleotide polymorphism of the CYP2C19 681G>A was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all the patients.Results CR was found in 126 patients(20.5%).There was CYP2C19 681G>A polymorphism in the study population.The frequencies of the three kinds of genotypes(GG,GA,A A) in CR group and non-CR (NCR)group were 32.5%,47.6%,19.8%and 48.0%, 45.0%,7.0%,respectively.The frequency of AA genotype was significantly higher in NCR group than that in CR group (OR =3.03,95%CI:1.889~5.784,P=0.003).The A allele carriers were more likely to develop clopidogrel resistance compared with that of G allele carriers(OR=1.85,95%CI: 1.392~2.459,P=0.002).Conclusions CYP2C19 681G/A polymorphism is associated with the risk of CR,and the A allele carriers may be a possible genetic susceptibility factor for patients with CR. Objectives Clopidogrel is a prodrug that has be be converted to an active metabolite by hepatic cytochrome P450 (CYP) isoenzymes to inhibit platelet aggregation. Individual variability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness. In this study , we sought to determine the association between the single nucleotide polymorphism of CYP 2C19 681G> A and the occurrence of clopidogrel resistance (CR) in Chinese. Methods The study enrolled 614 hospitalized patients who underwentsuccessful percutaneous coronary intervention with drug-eluting stents were received the treatmentwith dual antiplatelet regimen (aspirin plus clopidogrel). All patients received loading doses of 600 mg clopidogrel and 300 mg aspirin.20 μmol / L ADP-induced platelet aggregation ratio (PAR) was assessed 24 h after clopi- dogrel administration. 70% was defined as CR.Genomic DNA was extracted from whole blood sampl es according to standard protocols, the single nucleotide polymorphism of the CYP2C19 681G> A was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all the patients. Results CR was found in 126 patients (20.5%). There was CYP2C19 681G> A polymorphism in the study population. The frequencies of the three kinds of genotypes (GG, GA, AA) in CR group and non-CR (NCR) group were 32.5%, 47.6%, 19.8% and 48.0% 45.0%, 7.0%, respectively. The frequency of AA genotype was significantly higher in NCR group than that in CR group (OR = 3.03, 95% CI: 1.889-5.784, P = 0.003) develop clopidogrel resistance compared with that of G allele carriers (OR = 1.85, 95% CI: 1.392-2.459, P = 0.002) .Conclusions CYP2C19 681G / A polymorphism is associated with the risk of CR, and the allele carriers may be a possible genetic susceptibility factor for patients with CR.
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