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Study On The Application Of Gene And Platelet Function Detection For Individualized Dual Antiplatelet Therapy

Posted on:2019-06-03Degree:MasterType:Thesis
Country:ChinaCandidate:X HuangFull Text:PDF
GTID:2334330569995759Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Objective:To study Sichuan population CYP2C19(rs4244285,rs4986893),COX-1(rs1330344),COX-2(rs20417),GPIIIa(rs5918),PEAR1(rs1204331),P2Y1(rs1065776),GPIa(rs1126643),PAI-1(rs1799768)Frequency of Genes to Study the Association between the Polymorphism of the Site Gene and the Maximum Aggregation Rate of Platelets,and to Study the Application of Double Antiplatelet after Percutaneous Coronary Intervention in Patients with Gene Polymorphism and Coronary Atherosclerotic Heart Disease The efficacy of the drug and the relevance of adverse reactions.Try to explore drug gene detection and platelet function test in patients with coronary atherosclerotic heart disease after percutaneous coronary intervention after the application of dual antiplatelet drugs personalized medicine research and application.Method:Selection of Cardiology Department of Affiliated Hospital of UESTC from December 2016 to May 2017 Patients with coronary atherosclerotic heart disease undergoing percutaneous coronary intervention(PCI)for obtaining coronary atherosclerotic heart disease and obtaining clinical data and biochemistry Indicators,medication records,and other information,detected patients CYP2C19(rs4244285,rs4986893),COX-1(rs1330344),COX-2(rs20417),GPIIIa(rs5918),PEAR1(rs1204331),P2Y1(rs1065776),GPIa(rs1126643),PAI-1(rs1799768)9 gene polymorphisms of 8 genes,which were induced by arachidonic acid(AA)and adenosine diphosphate(ADP)on the next day and three months after PCI in patients.The aggregates were tested for the maximum platelet aggregation rate(MAR)and the patients were followed up for major cardiovascular events and adverse drug reactions at 3 months,6 months,and 9 months.Grouping according to genotypes,drugs,clinical data,etc.,and comparing the relationship between clinical data,relevant test and examination indicators,gene polymorphisms,drugs,cardiovascular events,and adverse drug reactions in different groups,attempting to double antiplatelet The individualized use of drugs provides favorable information and data references.Result:1.The nine genetic polymorphisms in this study were all consistent with Hardy-weinberg genetic balance test;2.The MAR-ADP of the clopidogrel and ticagrelor groups was 41.7±13.1 and 27.1±15.3,respectively,the next day after surgery,P<0.001.3.In the clopidogrel group and the ticagrelor group,the MAR-ADP at 3 months after operation was 40.4±11.6,26.4±11.1,respectively,P<0.001.The frequency of hemorrhagic events in the clopidogrel and ticagrelor groups at follow-up at 3,6 and 9 months was 26.4% and 60.7%,respectively,and 24.1% and 60.7%,25.8% and 60.7%,respectively,between the two groups.There was a significant difference in the incidence of follow-up bleeding(P<0.05).4.The MAR-AA of patients with different CYP2C19 genotypes were 18.0±10.1,20.4±8.0,P=0.439,MAR-ADP were 40.9±13.1,45.5±13.1,P=0.254,respectively.PAI-1 4G/4G type was related to the difference of aspirin's antiplatelet ability,P<0.05.GPIa CC type was related to the occurrence of cardiovascular events,P<0.001,indicating that non-GPIa CC patients were more likely to have cardiovascular events.5.PAI-1 gene 4G/4G type is related to the difference of antiplatelet ability of aspirin,P<0.05;6.The genotype CC of GPIa gene was associated with the occurrence of cardiovascular events,P<0.001.Conclusion:1.The maximal platelet aggregation rate in patients in the ticagrelor group was higher than that in the clopidogrel group,and the frequency of bleeding events was higher,suggesting that platelet function tests may have a predictive effect on bleeding events.2.There was no significant difference in MAR-AA and MAR-ADP between CYP2C19 fast-metabolized and slow-metabolized patients,suggesting that the difference in CYP2C19 genotype-responsive CYP2C19 drug-metabolizing enzyme activity had little difference in antiplatelet effect.3.The PAI-1 4G/4G type may reduce the antiplatelet effect of aspirin,suggesting that patients carrying this SNP need to optimize the treatment plan.4.The type of GPIa CC is related to the occurrence of cardiovascular events.Non-GPIa CC patients are more likely to have cardiovascular events.The association between GPIa CC and cardiovascular events is related to non-GPIa CC patients.
Keywords/Search Tags:Gene detection, Platelet Function Detection, Aspirin, Clopidogrel, Ticagrelor
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