Effects Of P2Y12 And CYP2C19 Gene Polymorphisms On Antiplatelet Effect Of Clopidogrel In Patients With Acute Cerebral Infarction

Objectives: To investigate the effects of polymorphisms of P2Y12 and CYP2C19 genes on the anti-platelet aggregation and clinical efficacy of clopidogrel in patients with acute cerebral infarction.The platelet activation markers CD62 P,PAC-1 and NIHSS scores were selected as the main evaluation indicators to analyze the difference of the indicators between patients with different P2Y12 and CYP2C19 genotypes after using clopidogrel.The purpose of this study is to provide more reference and basis for individualized treatment of patients with acute cerebral infarction.Methods:1.According to the case selection and exclusion criteria,111 patients diagnosed with acute cerebral infarction were selected from Internal Medicine-Neurology of First People's Hospital of Shangqiu City from December 2016 to November 2017.2.Polymorphisms of P2Y12 and CYP2C19 genes were detected in 111 patients with acute cerebral infarction who were included in the study by PCR-RFLP.According to whether there is mutation at the G52 T site on the P2Y12 gene,the selected patients were divided into G52 T mutation group and G52 T non-mutation group.According to CYP2C19 genotyping,the selected patients were divided into extensive metabolizer group(CYP2C19*1/*1,EM group),intermediate metabolizer group(CYP2C19*1/*2,CYP2C19*1/*3,IM group),poor metabolizer group(CYP2C19 *2/*2,CYP2C19 *2/*3 and CYP2C19 *3/*3,PM group).3.Flow cytometry was used to detect the positive expression rate of platelet activation markers CD62 P and PAC-1 in the selected patients before clopidogrel treatment,treatment day 7 and treatment day 14,and the expression level was expressed as positive expression rate.4.The National Institutes of Health Stroke Scale(NIHSS)was used to assess the severity of neurological impairment before clopidogrel treatment,7 days after treatment and 14 days after treatment.5.Statistical analysis was performed using SPSS 20.0 software.The intra-group and intra-group differences of the platelet activation markers CD62 P,PAC-1 expression level and NIHSS scores before and after treatment were compared between the groups.So as to evaluate the correlation between P2Y12 and CYP2C19 gene polymorphisms in patients with acute cerebral infarction and the anti-platelet effect and clinical efficacy of clopidogrel.Results:1.Among the 111 patients with acute cerebral infarction in this study,36 patients were in the G52 T mutation group,accounting for 32.4%,75 patients were in the G52 T non-mutation group,accounting for 67.6%;There were 42 patients in the extensive metabolizer group,accounting for 37.8%,There were 53 patients in the intermediate metabolizer group,accounting for 47.7%,and 16 patients in the poor metabolizer group,accounting for 14.5%.2.There was no significant difference in platelet activation markers CD62 P,PAC-1 expression and NIHSS score between the two groups before using clopidogrel(P > 0.05).Compared with before treatment,on the 7th and 14 th day after treatment,platelet CD62 P,PAC-1 expression and NIHSS scores in G52 T mutation group,G52 T non-mutation group,extensive metabolizer group and intermediate metabolizer group decreased significantly(P < 0.05),while platelet CD62 P and PAC-1 expression levels in poor metabolizer group decreased,but there was no significant difference(P > 0.05).3.On the 7th and 14 th day after treatment,there was no significant difference in platelet CD62 P,PAC-1 expression and NIHSS score between G52 T mutant group and G52 T non-mutant group(P > 0.05);platelet CD62 P and PAC-1 expression levels in poor metabolizer group and intermediate metabolizer group were significantly higher than those in extensive metabolizer group(P < 0.05);the NIHSS score in poor metabolizer group was significantly higher than that in extensive metabolizer group(P < 0.05).Conclusions:1.The polymorphism of CYP2C19 gene is closely related to the anti-platelet aggregation and clinical efficacy of clopidogrel in patients with acute cerebral infarction.The anti-platelet aggregation and clinical efficacy of clopidogrel in the extensive metabolizer group are the best,followed by the intermediate metabolizer group and the poor metabolizer group.The use of clopidogrel can be reasonably selected according to the CYP2C19 genotype of patients.2.The G52 T polymorphism of P2Y12 gene in patients with acute cerebral infarction may have no significant correlation with the antiplatelet effect of clopidogrel.