Study On Individualized Medication Of Clopidogrel Based On Genetic Factors(CYP2C19?CES1) And Combined Medication Factors

Background: Cerebral infarction,cerebral thrombosis,coronary heart disease,myocardial infarction,atherosclerosis and other cardiovascular and cerebrovascular diseases take the lives of about 12 million people worldwide every year,surpassing malignant tumors.Mean-while cardiovascular and cerebrovascular diseases have become healthy "number one killers".Clopidogrel,as the most commonly used P2Y12 receptor inhibitor,is widely used in clinic.However,studies found that about 4% to 30% of patients did not achieve the expected anti-platelet effect after applying conventional doses of clopidogrel and developed clopidogrel resistance(CR).Clopidogrel resistance can increase the risk of stent thrombosis,acute myocardial infarction,and target vessel revascularization.In severe cases it can lead to death.The US Food and Drug Administration(FDA)and the American College of Cardiology/American Heart Association(ACCF/AHA)have issued warnings for the clinical application of clopidogrel.The appearance of clopidogrel resistance is associated with a variety of factors,including genetic and non-genetic factors.Objective: Based on genetic factors(CYP2C19,CES1)and co-administration factors,this study explored the factors influencing the individual administration of clopidogrel and provided a basis for the individualized medication of clopidogrel.Method: In this study,the maximum platelet aggregation rate(MAR)was used as the evaluation index.The patients who took clopidogrel for 5 days were included.The CYP2C19 and CES1 genotypes were detected.The combined medication information of the patients were collected to evaluate the effect of genetic factors(CYP2C19 and CES1)and combined medication factors on clopidogrel.(1)Screen patients who met the inclusion criteria from March 2018 to June 2019 in the People's Hospital of Zhengzhou University(Henan Provincial People's Hospital),collect the maximum platelet aggregation rate(MAR)within 5 days.(2)A platelet function analyzer(PL-16)was used to monitor the maximum platelet aggregation rate(MAR),DNA was extracted through a whole blood DNA extraction kit,concentration and quality of the extracted DNA were tested by ABI nanodrop one microphotometer.(3)The technology of gene chip was used to test CYP2C19,and the multiplex PCR targeted capture technology was used to test the single nucleotide polymorphism site(SNPs)of CES1.(4)Retrieve the electronic medical record system,collect patient demographic data,combined medication data,combined diseases,laboratory tests and other information.Establish a database.(5)Use IBM SPSS Statistics 23.0 statistical software for data analysis.Statistical description of measurement data is expressed by(x±s),comparison between groups is by two-sided t test;count data is expressed by frequency and composition ratio(%).The count data is expressed by frequency and composition ratio(%),and the comparison between groups is tested by x2.In univariate analysis,non-parametric tests were used for comparison among groups(Mann-Whitney U test between 2 groups,Kruskal-Wallis analysis for 3 groups),and Spearman correlation test was used for correlation between quantitative data,P< 0.05 is represented for statistically significant.The ?2 test was used to perform Hardy-Weinberg equilibrium test on the genotyping results of three sites in this study.P>0.05 was considered to be in line with Hardy-Weinberg equilibrium.Use SHE sis online software for chain imbalance analysis,and judge the chain imbalance according to the output result of SHE sis.Results: Multivariate analysis showed that genetic factors(CYP2C19 gene polymorphism),combined medication factors(Danshenchuanqiongzine injection(Z=2.200,P=0.03),alprostadil(Z=2.286,P=0.02)and metoprolol(Z=2.059,P=0.04))were correlated with the maximum platelet aggregation rate of patients.Multivariate analysis did not find a significant correlation between age,body mass index,renal function,diabetes,smoking,routine biochemical indicators and the maximum platelet aggregation rate.Conclusion: Clopidogrel's pharmacodynamics is affected by a variety of factors.In details,genetic factors(CYP2C19 gene polymorphism),combined medication factors(Danshenchuanqiongzine injection,alprostadil and metoprolol)have an effect on clopidogrel antiplatelet efficacy.