Measurement Of CYP2C19 Gene Polymorphisms And The Correlated Prognosis Of Clopidogrel–treated Patients With Coronary Heart Disease

Objective: To investigate the distribution of CYP2C19 genotype in clopidogrel-treated patients,and to study the correlation between CYP2C19 gene polymorphism,the primary adverse cardiac events(MACE),and stent thrombosis reformation.Methods: 333 patients hospitalized in cardiovascular internal medicine department from July 2013 to October 2014 were accepted for percutaneous coronary intervention(PCI).Patients were given 75 mg clopidogrel orally in the maintenance treatment.Allele of CYP2C19*1,*2,*3 was measured using PCR-RFLP and taq Man polymerase chain reaction.Out-patient follow-up was carried out through phone call or via diagnose in out-patient department,statistically analyze the primary clinical endpoint events of clopidogrel-treated patients in 12 monthclinical prognosis,including cardiac death,myocardial infarction,reascularization.The correlation between CYP2C19 gene polymorphism and the secondary clinical endpoint events including stent thrombosis and cerebral apoplexy were analyzed.Results: Among 333 enrolled patients the wild type *1/*1(681GG/636GG)gene were found in 140 cases(accounted for about 42%);heterozygous type *1/*2(681GG/636GA)gene was found in 125 cases(account for about 37.5%),*1/*3(681GA/636GG)gene was found in 19 cases(accounted for about 5.7%);homozygous mutant type *2/*2(681GG/636AA)gene was found in 37 cases(accounted for about 11.1%),*2/*3(681GA/636GA)gene was found in 11 cases(accounted for about 3.3%),and *3/*3(681AA/636GG)gene was 1 case(accounted for about 0.3%).Strong metabolic type(*1/*1)was 42.0%,intermediate metabolic type(*1/*2,*1/*3)was 43.2%,the weak metabolic type(*2/*2,*2/*3,*3/*3)was 14.7%.A total of 49 clinical endpoint events were found by clinical follow-up.Among them,41 cases(83.7%)was the primary adverse clinical endpoint events including strong metabolic type including 22 cases(28.6%)and intermediary/weak metabolic types including 19 cases(38.8%),with the occurrence ratio of(28.6%)vs(38.8%),P>0.05(no statistical significance).Another 8 cases(16.3%)were secondary clinical endpoint events including the strong metabolic type in 3 patients(6.1%),intermediary/weak metabolic types,5 cases(10.2%),with occurrence ratio of(6.1%)vs(10.2%),P<0.05(statistical significance).Logistic regression analysis of major clinical adverse events related factors found that smoking(P=0.037;95%CI 0.25-20.7,OR= 16.2),type 2 diabetes mellitus(P=0.048;95%CI 1.01-27.13,OR=17.35),and CYP2C19 genotype(P=0.03;95%CI 1.08-9.37,OR=24.65)were correlated with MACE and are statistically significant.Conclusion: CYP2C19 gene polymorphisms is associated with the prognosis of clopidogrel-treated patients with coronary heart disease.Patients carrying one functional deletion allele is correlated with the risk of the incidence of stent thrombosis the secondary to the probability of clinical endpoint events compared with the patients with wild-type CYP2C19 genotype.Patients with a history of smoking and/or diabetes with CYP2C19 functional deletion allele have higher risk of primary clinical adverse end point events than nonsmoking patients,non-diabetes,and wild type CYP2C19 patients.