Relationship Between CYP2C19 Polymorphisms With Residual Platelet Reactivity And Prognosis In Clopidogrel-treated Patients After PCI

Objective:To explore relationship between CYP2C19* 2 and * 3 polymorphisms with residual platelet reactivity and adverse clinical events in clopidogrel-treated patients after percutaneous coronary intervention( PCI).Methods: Between April 2013 and November 2014, 519 consecutive CHD patients undergoing uneventful elective PCI in the Fujian Provincial Hospital were enrolled in this study,and Basic clinical information were recorded.Using DNA microarray chip method to detect CYP2C19 gene in all selected patients. According to CYP2C19 genotype, patients were divided into Extensive Metabolizer(EM); Intermediary Metabolism(IM).and Poor Metabolism(PM). Residual platelet aggregation was measured by optical turbidity and s CD40 L, s P-selectin were measured by ELISA at 24 hours after PCI. Compared the differences between the three groups of the three indicators and explore relationship between CYP2C19 genetic variation and ofthe three indicators.The patient’s follow-up was carried out through telephone, outpatient service and readmission records. The study endpoint is 1 year Major Adverse Cardiac events(MACE) after PCI, including Cardiac death, Nonfatal myocardial infarction and Rehospitalization due to Unstable angina(UA). Compare the incidence of MACE within 1 year among three groups andanalyzes the relationship between CYP2C19 gene polymorphisms and MACE.Results:(1)Among the patients included into the study and follow-up, 181 patients(34.9%)are extensive metabolizers(EM),(CYP2C19 *1/ *1).253 patients(48.8%) are intermediate metabolizers(IM),(CYP2C19 *1/ *2、CYP2C19 *1/ *3). 85patients(16.4%) are poor metabolizers,(PM),(CYP2C19 *2/ *2、CYP2C19*2/ *3、CYP2C19*3/ *3).(2) 24 hours after PCI, the IM and PM groups residual platelet aggregation were higher than the EM group: 15.89(27.90) 、 23.39(27.73) vs 8.58(17.47), the differences were statistically significant(P <0.05). the IM and PM groups s CD40 l levels were higher than those in EM group: 8819.5(4488.0) 、 8440.0(5906.0) vs 7989.1(4397.4),the difference was statistically significant(P <0.05). the IM and PM groups s P-selectin levels also higher than the EM group: 11.03(6.08) 、 11.89(6.89) vs 9.31(5.99),the difference was statistically significant(P <0.05).(3) Binary linear correlation analysis showed that CYP2C19 * 2, * 3 gene mutation have a statistically positive correlation with residual platelet activity,s CD40 L, s P-selectin,indicating a positive correlation, all P <0.05.(4)Result of clinical follow-up: 1patient Cardiac death( in EM group);9 patients Nonfatal myocardial infarction(1 in EM group, 6 in IM group, 2 in PM group); 59 patients met with Rehospitalization due to UA(12 in EM group,39 in IM group,8 in PM group).There are differences in the incidence of Rehospitalization due to UA among three groups(P <0.05). IM group and the PM group unstable angina readmission rates were 15.4%, 9.4%, compared with EM group(6.6%) was significantly higher.However, no significant difference was observed in the incidence of Cardiac death、Nonfatal myocardial infarction among three groups. At the same time, the incidence of the composite end point of MACE was higher in CYP2C19 *2 or *3 loss of function allele carriers(IM + PM group) when compared with non-carriers(EM),(P <0.05). Using Logistic regression model to analyze the related factors influencing the MACE and found there was a correlation between CYP2C19 polymorphisms and MACE(OR=2.524,95%CI 1.332-4.780,P=0.005).Conclusion:CYP2C19 * 2 or * 3 gene mutations impair the efficacy of clopidogrel antiplatele,cause high residual platelet reactivity after PCI, and CYP2C19 * 2 or * 3 allele loss of function carriers have increased incidence of adverse cardiovascular events.