Study On CYP2C19 Gene Polymorphism And Thromboelastogram In The Monitoring Of Clopidogrel Responsiveness In Coronary Heart Disease

Objective In patients with coronary heart disease who underwent PCI,someone experienced low clopidogrel responsiveness,and antiplatelet therapy failed achieve the desired effect.This study analysed the correlation between CYP2C19 gene polymorphism and clopidogrel responsiveness detected by thromboelastography,to explore the value of gene test and thromboelastography in the monitoring of clopidogrel responsiveness,and provide strong support and evidence-based basis for guiding the selection of clinical antiplatelet drug treatment options.Methods From January 2017 to December 2019,799 patients with coronary heart disease after PCI who were hospitalized in the Affiliated Hospital of Qingdao University were chosen as the research objects.According to the results of the thromboelastogram adenosine diphosphate(ADP)receptor inhibition rate,the patients were divided into clopidogrel low responsiveness group and clopidogrel sensitive responsiveness group.At the same time,detect CYP2C19 gene polymorphism using the pyrosequencing method.Analyzing the relationship between CYP2C19 gene polymorphism and clopidogrel responsiveness,as well as the significance in monitoring clopidogrel responsiveness and diagnosing bleeding and coagulation risks,and the long-term MACE.Results (1)Comparing the clopidogrel low responsiveness group and the clopidogrel sensitive responsiveness group,there were no statistically significant differences in BMI index,history of drinking,hypertension,hyperlipidemia and diabetes(P>0.05);and there were statistically significant differences in age,height,weight,gender,smoking history and CYP2C19 gene type(P<0.05).(2)The result of Logistic regression analysis showed that gender and CYP2C19 gene type were the independent influencing factors of clopidogrel responsiveness(P<0.01).(3)Distribution of CYP2C19 alleles in the population of this study: CYP2C19*1 was dominant,accounting for 67.2%.CYP2C19*2(28.10%)and CYP2C19*3(4.88%)were the common mutant genes.The CYP2C19 gene rapid metabolic type accounted for 44.18%(n=353),the CYP2C19 gene intermediate metabolic type accounted for 45.68%(n=365),and the CYP2C19 gene slow metabolic type accounted for 10.14%(n=81).(4)Incidence rate of clopidogrel resistance: There were significant differences among the three CYP2C19 gene types(P<0.05).Pairwise comparison,the difference between the rapid metabolic type and the intermediate metabolic type was not significant(P>0.05);the clopidogrel resistance rate of the rapid metabolic type was significant lower than that of the slow metabolic type,with statistically difference(P<0.01);and the clopidogrel resistance rate of the intermediate metabolic type was lower than that of the slow metabolic type,with statistically significant difference(P<0.05).(5)ADP inhibition rate: There were significant differences among the three CYP2C19 gene types(P<0.001).Compared with each other,there was no significant difference between the rapid metabolic type and the intermediate metabolic type(P>0.05);there was statistically significant difference between the rapid metabolic type and the slow metabolic type,the ADP inhibition rate of the slow metabolic type was lower(P<0.001);and there was statistically significant difference between the intermediate metabolic type and the slow metabolic type,the ADP inhibition rate of the slow metabolic type was lower(P<0.01).MA-ADP value: There were significant differences among the three CYP2C19 gene types(P<0.01).Compared with each other,the MA-ADP value of the rapid metabolic type and the intermediate metabolic type was no significant difference(P>0.05);there was statistically significant difference between the rapid metabolic type and the slow metabolic type,the MA-ADP value of the slow metabolic type was higher(P<0.01);and there was statistically significant difference between the intermediate metabolic type and the slow metabolic type,the MA-ADP value of the slow metabolic type was higher(P<0.05).(6)AUC of ADP inhibition rate was0.6238,P<0.001.AUC of MA-ADP value was 0.6118,P<0.01.(7)There was statistically significant difference of MA-ADP value between the clopidogrel low responsiveness group and the clopidogrel sensitive responsiveness group.Compared with the clopidogrel sensitive responsiveness group,the proportion of patients with MA-ADP value less than31 mm and in the range of 31-47 mm was lower(P<0.05)in the clopidogrel low responsiveness group;the proportion of patients with MA-ADP value more than 47 mm was higher(P<0.05)in the clopidogrel low responsiveness group.(8)Follow up for half a year,excluding 32 patients who were lost to follow-up,collect the number of patients with unstable angina pectoris and acute myocardial infarction.The clopidogrel low responsiveness group had a higher incidence,and there was a statistical difference(P<0.001).Conclusion (1)There is a correlation between CYP2C19 gene polymorphism and clopidogrel responsiveness.CYP2C19*2 and CYP2C19*3 mutation genes significantly increase clopidogrel resistance.(2)CYP2C19 gene polymorphism detection and thromboelastogram have good consistency in the assessment of clopidogrel responsiveness,which can be used to guide the choice of clinical antiplatelet therapy.(3)Thromboelastogram has certain value in prompting the bleeding,thrombosis risks and occurrence of long-term MACE.