摘要
Abstract
Background There are general individual differences in the clinical efficacy of clopidogrel,which is related to race and affected by genotype.Objective To investigate the correlation of CYP2C19 genetic polymorphism with clopidogrel resistance and prognosis in patients with acute coronary syndrome(ACS) in order to provide a basis for individualized antiplatelet therapy guided by genotyping.Methods From March to December 2012,98 consecutive patients with ACS who were hospitalized at the Department of Cardiology of Aerospace Central Hospital were enrolled.After admission,patients were given clopidogrel at a first dose of 300 mg and then 75 mg/d orally,or administered directly at a regular dose of 75 mg/d.The platelet aggregation rate,platelet inhibition rate and clopidogrel resistance in all ACS patients were evaluated at the time of admission and after a clopidogrel therapy of 3 days.Meanwhile,CYP2C19 gene polymorphisms were determined by Taqman-PCR.Based on CYP2C19 gene test results,according to whether or not the mutant gene A was carried,patients were divided into wild-type group(without mutant gene A in both G681A in fifth exon and G636A in fourth exon,n=34) and mutant group(with mutant gene A in either G681A in fifth exon or G636A in fourth exon,n=64).Follow-up was applied,and major adverse cardiovascular events(MACEs) were recorded.Results The genotypes of CYP2C19*2 and CYP2C19*3 were in accordance with Hardy-Weinberg′s law of equilibrium(P>0.05),which suggested that the sample included in the study had a good population representativeness.There was no significant difference in baseline platelet aggregation rate between the patients with different CYP2C19*2 genotypes(P>0.05).In genotype CYP2C19*2 patients,clopidogrel resistance rate was significantly higher in GA patients than in GG patients after 3 days′ clopidogrel therapy(P<0.05),and clopidogrel resistance rate was significantly higher in AA patients than in GG and GA patients after 3 days′ clopidogrel therapy(P<0.05).In genotype CYP2C19*2 patients,GA and AA patients had lower platelet inhibition rate than GG patients(P<0.05).In CYP2C19*2 patients,the platelet aggregation rate in GG and GA genotype patients after clopidogrel therapy of 3 days was less than that at admission(P<0.05).There was no significant difference in platelet aggregation rate at admission,platelet aggregation rate after 3 days of treatment and platelet inhibition rate in different CYP2C19*3 genotype patients(P>0.05).In CYP2C19*3 genotype patients,the platelet aggregation rate in GG and GA genotype patients after clopidogrel therapy of 3 days was less than that at admission(P<0.05).Compared with mutant group,wild-type group had lower clopidogrel resistance(P<0.05);compared with mutant group,wild-type group had lower lower MACEs(P<0.05).In genotype CYP2C19*2 patients,GG patients had lower incidence of MACEs than AA patients(P<0.05),and GA patients had lower incidence of MACEs than AA patients(P<0.05).There was no significant difference in the incidence of MACEs in genotype CYP2C19*3 patients(P>0.05).Conclusion CYP2C19 gene polymorphism was associated with antiplatelet effects of clopidogrel in patients with ACS.Patients with CYP2C19 fifth exon mutation had reduced antiplatelet effects and poor prognosis after receiving conventional dose of clopidogrel,but the fourth exon mutation had relatively little effect on the prognosis of the patients.关键词
急性冠状动脉综合征/细胞色素P450酶系统/多态性,单核苷酸/血小板聚集抑制剂/血小板聚集/预后/CYP2C19/氯吡格雷Key words
Acute coronary syndrome/Cytochrome P-450 enzyme system/Polymorphism/single nucleotide/Platelet aggregation inhibitors/Platelet aggregation/Prognosis/CYP2C19/Clopidogrel分类
医药卫生
