Impacts Of CYP2C19 Gene Polymorphism On Anti-platelet Efficacy In Patients Taking Clopidogrel After PCI Operation

Objective: To predict the anti-platelet value of CYP2C19 gene polymorphism in patients with acute coronary syndrome(ACS) and taking clopidogrel after PCI operation via studying platelet activation markers CD62 P and PAC-1 expression rate in patients with three different phenotypes of CYP2C19 before and after administering clopidogrel and investigating the distribution in clopidogrel resistance group in three different metabolic type patients.Methods:1.A total of 104 patients with ACS in administration of clopidogrel for the first time between March 2014 and October 2015 at Department of Cardiology, Yanan University Affiliated Hospital were enrolled in this study as experimental subjects.2.Blood specimens were collected and submitted to Shanxi Baimei Medical Laboratory for CYP2C19 gene tests after admitting. Subjects were divided into three groups according test results: extensive metabolizer group(EM) with 40 patients, namely CYP2C19 *1/ *1; intermediary metabolizer group(IM) with 49 patients, namely CYP2C19 *1/ *2 and CYP2C19 *1/ *3; poor metabolizer group(PM) with 15 patients,namely CYP2C19 *2/ *2, CYP2C19*2/ *3 and CYP2C19*3/ *3.3.Three groups of patients were respectively given clopidogrel 600 mg with preoperative loading dose and postoperative maintenance dose 75 mg/d. Venous blood was drawn and submitted at 24 h before and after administration respectively. Platelet activation markers CD62 P and PAC-1 expression rate was tested at 24 h before and after administration by FCM among three groups. CD62 P and PAC-1 expression changes were compared among three groups.4.CD62 P and PAC-1 expression rate was worked out according to semi-guartile range method. Clopidogrel resistance was defined as significantly increased(CD62p>15. 5%and PAC-1>3.01%) expression in both of them. The distribution of clopidogrel was compared among three groups in patients with different metabolic types.Results:1.General data comparisons among three groups: including sex, age, CHD factors(history of hypertension, diabetes and smoking), lipids, family history of CHD, BMIand other conventional biochemical indexes: blood platelet count, creatinine and D-dimer.The difference of general data has no statistical significance(P>0.05).2.The difference in drug combination has no statistical significance(P>0.05)among three groups.3.The difference in coronary artery pathological conditions has no statistical significance(P>0.05)among three groups.4.Comparisons of platelet activation markers CD62 P and PAC-1 expression rate before and after taking clopidogrel among three groups: CD62 P and PAC-1 expression rate before taking clopidogrel has no statistical significance(P>0.05) among three groups.CD62 P and PAC-1 expression rate is declined to some extent 24 hours after taking clopidogrel compared to before taking clopidogrel. Compared CD62 P and PAC-1expression rate in EM group with IM group and PM group, the difference has statistical significance(P<0.05). Compared CD62 P and PAC-1 expression rate in IM group with PM group, the difference has no statistical significance(P>0.05).5.Comparisons of platelet activation markers CD62 P and PAC-1 expression decreases before and after taking clopidogrel among three groups: CD62 P and PAC-1 expression decreases have statistical significance(P<0.05) among three groups. Compared CD62 P and PAC-1 expression decreases in EM group with IM group and PM group 24 hours after taking clopidogrel, the difference has statistical significance(P<0.05). Compared CD62 P and PAC-1 expression decreases in IM group with PM group, the difference has no statistical significance(P>0.05).6.Comparisons of distribution of clopidogrel among three groups in patients with different metabolic types: The distribution of clopidogrel among three groups in patients with different metabolic types has statistical significance(P<0.05). The distribution in patients of CR group has statistical significance(P<0.017) compared to EM group and IM group. The distribution in patients of CR group has statistical significance(P<0.017)compared to EM group and PM group. The distribution in patients of CR group has no statistical significance(P>0.017) compared to IM group and PM group.Conclusion:1. Clopidogrel can suppress platelet activation markers CD62 P and PAC-1 expression.2. The inhibiting capacity of platelet activation markers CD62 P and PAC-1 expression in EM group is stronger than that of IM group and PM group.3. The possibility of clopidogrel resistance in IM group and PM group is greater than that of EM group.