The Relationship Of Clopidogrel Responsiveness With Cytochrome P4502C19 Gene Polymorphism And The Leve Of Eets In Patients With Acute Coronary Syndrome

ObjectiveTo assess the relations of low clopidogrel responsiveness and cytochrome P4502C19?CYP2C19?gene polymorphism and other risk factors of acute coronary syndrome?ACS?,To investigate the role of epoxyeicosatrienoic acids?EETs?in predictingcy tocytochrome P₄₅₀2C19?CYP2C19?genetype,To investigate the relationship between the level of EETs in human plasma and the severity of coronary artery stenosis and the inhibition rate of platelet aggregation in patients with ASC.MethodsA total of 123 patients with ACS receiving aspirin and clopidogrel dual antiplatelet were enrolled.We detected the CYP2C19 genotype,platelet aggregation inhibition rate and the concentration ofEETs in all selected patients.According to the results of CYP2C19 gene polymorphism,the patientswas divided into three groups:fast metabolic type with CYP2C19*1/*1,medium metabolic type with CYP2C19*1/*2 and CYP2C19*1/*3,and slow metabolism type with CYP2C19*2/*2,CYP2C19*2/*3 and CYP2C19*3/*3.The Clinical characteristics,the concentration ofEETs and platelet aggregation inhibition rates were compared betweenthree groups.The inhibition rate of platelet aggregation was measured by using thromboelastography?TEG?.According to the results,the distribution of CYP2C19genepolymorphism was compared between clopidogrel low response group?PAIR<50%?and clopidogrel sensitive group?PAIR?50%?.The Clinical characteristics,the concentration of EETs and platelet aggregation inhibition rates were compared between three groups.Logistic regression analysis was used to analyze the relationship between clinical factors and LCR.A ROC curve was used to evaluate the efficacy of human plasma level of EETs in predicting the genotype of CYP2C19.The degree of coronary stenosis was evaluated by Gensini score,and the correlation between EETs level and the degree of coronary artery stenosis and the inhibition rate of platelet aggregation in patients with ACS was analyzed by Pearson correlation coefficient.ResultsThere were significant differences in the content of EETs and platelet aggregation inhibition rates between the fast metabolism,the intermediate and the slow metabolism of CYP2C19 gene,and the difference was significant statistically?P<0.05?.The distribution of CYP2C19 gene polymorphism was statistically significant between LCR and NCR,the number of patients with LCR in the slow metabolism was higher than that in the other groups.Logistic regression analysis showed that the Slow metabolism of CYP2C19 gene and lower EETs level were risk factors for LCR.The area under the ROC curve?95%CI:0.791-0.965?was 0.893?AUC,P<0.05?by using human plasma EETs level to predict the CYP2C19 genotype.When the level of EETs was the best predictive critical value?40.12pg/ml?,the sensitivity,the specificity the positive predictive value and the negative predictive value were 81.9%,88.9%,54%and97%,respectively.Plasma EETs level was positively correlated with the inhibition rate of platelet aggregation r=0.295 95%CI:0.108—0.454,P=0.001).Plasma EETs level was negatively correlated with the severity of coronary artery stenosis?r=-0.462 95%CI:-0.630—-0.292,P<0.01?,we can see that the higher the degree of coronary stenosis,the lower the level of plasma EETs.ConclusionThe Slow metabolism of CYP2C19 gene and lower EETs level were risk factors for LCR.When the level of plasma EETs in patients with ACS is 40.12pg/ml,we should consider the detection of CYP2C19 genotypes,and provide guidance for the individual treatment of antiplatelet therapy.