Correlation Study Of Antiplatelet Drug Gene Polymorphism With Platelet Aggregation Rate And Thrombotic Events After PCI

Objective:For the patients treated with clopidogrel and aspirin after PCI,we aimed to investigate the correlation of CYP2C19,COX-1,COX-2,GPIIIa,PEAR1,P2Y1,GPIa,PAI-1 gene polymorphism and serum biochemical indexes with platelet aggregation rate and thrombotic events.Methods:In this study,171 patients were included who underwent percutaneous coronary intervention(PCI)in the Department of Cardiovascular Medicine,The First Hospital of Jilin University from April 2020 to December 2020.4 patients were excluded.The remaining 167 patients were followed up for 6 and 12 months,Eight of them lost their visits,The remaining 159 patients.Demographic data [Sex,Age] and blood biochemical data [total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),and glutamyltranspeptidase(γ-GGT),creatinine(Cr),urea nitrogen(BUN),fasting blood glucose(Glu)] were collected.COX-1,COX-2,GPIIIa,PEAR1,P2Y1,GPIa and PAI-1 genotype polymorphisms were detected in 167 patients.CYP2C19 gene was detected in 119 patients.ADP-induced platelet aggregation rate of patients with CYP2C19 genotype was measured after taking aspirin and clopidogrel for 7 days.The AA-induced platelet aggregation rates were detected by COX-1,COX-2,GPIIIa,PEAR1,P2Y1,GPIa and PAI-1 genotypes.At 1 year follow-up,the outcome was thrombosis.Thrombotic events were defined as acute,chronic thrombotic and all-cause deaths confirmed by coronary angiography.The patients with aspirin 100mg/day maintenance dose for 1 year were selected.To explore the effects of COX-1,COX-2,GPIIIa,PEAR1,P2Y1,GPIa,PAI-1 genotype polymorphism and other factors on platelet aggregation of AA and ADP in univariate logistic regression model.COX regression model was used to analyze the correlation of aspirin gene polymorphism,serum biochemical indices and other factors with thrombotic events.IBMSPSS 25.0and Graph Pad Prism 5 were used for statistical analysis.Results and Conclusions:1.119 patients were tested for CYP2C19 geno type polymorphism,including CYP2C19 *1/*1(55 cases),CYP2C19 *1/*2,*1/*3(44 cases),CYP2C19 *2/*2,*2/*3,*3/*3(20 cases).COX-1,COX-2,GPIIIa,PEAR1,P2Y1,GPIa and PAI-1genotype polymorphisms were detected in 167 patients.Among the COX-1genotypes,24 cases were wild-type,68 cases were homozygous,and 75 cases were heterozygous.Among COX-2 genotype patients,153 cases were wildtype,1 case was homozygous,and 13 cases were heterozygous.Among GPIIIa genotypes,164 cases were wild,and 3 cases were heterozygous.Among PEAR1 genotyping,76 cases were wild type,20 cases were homozygous,and 71 cases were heterozygous.Among P2Y1 genotypes,144 cases were wild,and 23 cases were heterozygous.Among GPIa genotypes,72 cases were wild type,20 cases were homozygous,and 75 cases were heterozygous.Among THE PAI-1 genotypes,58 cases were 4G/4G,79 cases were4G/5G,and 30 cases were 5G/5G.2.The platelet aggregation rate in CYP2C19 geno type slowed,(CYP2C19 *1/*1)34.30±17.83,(CYP2C19 *1/*2,*1/*3)39.29 ±19.34,(CYP2C19 *2/*2,*2/*3,*3/*3)49.83±18.44,The differences among the three groups were statistically significant(P=0.030).The poor metabolism group was significantly higher than that in extensive metabolism group(P=0.008).3.In COX-1,COX-2,GPIIIa,PEAR1,P2Y1,GPIa and PAI-1 geno types,AA induced platelet aggregation rate was 24.92±25.54 in PEAR1 GG group and15.55±17.16 in GA+AA group.The platelet aggregation rate in GG group was significantly higher than that in GA+AA group,the difference was statistically significant(P=0.015).In the detection of ADP-induced platelet aggregation rate,P2Y1 CC group 40.78±20.51,CT group 51.81±20.30,CT group was higher than CC group,the difference was statistically significant(P=0.042).4.Platelet aggregation rate <30% is a decrease in platelet aggregation rate.Univariate logistic regression analysis showed that PEAR1 GA+AA genotype polymorphism,female and statin therapy had a protective effect on AA platelet aggregation,Because all three groups reduced platelet aggregation rates(OR=0.315,P=0.026;OR=0.097,P=0.026;OR=0.285,P=0.010).Creatinine value greater than80 umol/L was significantly correlated with Increase platelet aggregation rate(OR=3.652,P=0.009).PEAR1 GA+AA geno type polymorphism was associated with decreased ADP platelet aggregation(OR=0.364,P=0.025).Statin therapy was associated with decreased ADP of platelet aggregation(OR=0.212,P=0.007).5.COX regression analysis showed that hyperglycemia(fasting blood glucose >6.11 mmol/L)was associated with thrombotic events(OR=3.686,P=0.045).Gene polymorphism(COX-1,COX-2,GPIIIa,PEAR1,P2Y1,GPIa,PAI-1),gender,age and other serum biochemical indexes were not statistically significant,and there was no correlation with thrombotic events.6.Logistic regression analysis showed that PEAR1 gene polymorphism was associated with hyperglycemia,and the glucose in PEAR1 GA+AA group was higher than that in GG group(OR=2.054,P=0.025).