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Clinical Research On Detection Of CYP2C19 And PON1 Gene Polymorphisms In Yunnan Province Guiding Anti-platelet Therapy After PCI In Patients With ACS

Posted on:2020-01-19Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q YangFull Text:PDF
GTID:2404330602954482Subject:Pharmaceutical
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Objective:To analyze the CYP2C19 and PON1 gene polymorphisms in patients with acute coronary syndrome in Yunnan.To investigate the effect of anti-platelet precision therapy on clinical outcomes in patients with ACS after PCI based on CYP2C19 gene polymorphism,and the association between stent thrombosis and PON1 gene polymorphism.This study could further improve and supplement the Correlation studies between clopidogrel personalized treatment and CYP2C19 and PON1 gene polymorphisms,in order to provide theoretical guidance for future clinical treatment and improve clinical prognosis and patient's quality of life.Method:From January 2017 to June 2018,ACS hospitalized patients who were successfully performed PCIin the Department of Cardiology,the First People's Hospital of Kunming,and tested CYP2C19 and PON1 gene were selected as subjects based on inclusion and exclusion criteria.Genotyping of the CYP2C19*2,CYP2C19*3 and PON1 allele was performed by conventional polymerase chain reaction(PCR).We Followed up the patients to record adverse cardiovascular events and hemorrhagic complications occurred within 6 months and 12 months.Statistical analysis was performed using SPSS 17.0 software.All measurement data,depending on whether the data was subject to a normal distribution,were analyzed by T test or variance test.Data analysis of the count data was performed using the Pearson chi-square test.We tested the population representativeness of samples using Hardy-Weinberg equilibrium law.We used a two-class logistic regression analysis to explore the correlation between the incidence of adverse cardiovascular events and various factors.Mapping was performed by GraphPad Prism 6 software.Results:1.A total of 520 patients were included in the study.Among the results of CYP2C19*2 and CYP2C19*3 gene polymorphisms,extensive metabolizers(*1/*1):193 cases,intermediate metabolizers(*1/*2,*1/*3):262 cases,poor metabolizers(*2/*2,*2/*3,*3/*3):65 cases.The metabolic types were mainly EM and IM.The allele distributions of CYP2C19*2,CYP2C19*3 and PON1 genes were consistent with the Hardy-weinberg genetic equilibrium law,being representative of the population.The frequency of CYP2C19*2 and CYP2C19*3 alleles in Yunnan was statistically different from that in the United States and the United Kingdom,and there was no statistical difference compared with other regions in China.Among the PON1 allele frequencies,there were statistical differences between Yunnan and the UK,and there was no statistical difference between Yunnan and Beijing,Nanjing,Japan,and the United States.2.The follow-up results of 520 patients with ACS showed that there was no significant difference in the incidence of MACE?adverse cardiovascular events and hemorrhagic complications among the precision therapy groups for 6 months and 12 months.There were statistical differences in the incidence of all adverse cardiovascular events bet:ween the 6-month and the 12-month therapies in EM?IM?PM?GG?GA+AA groups.There were significant differenees in the incidence of chest tightness and chest pain events between the 6-month and the 12-month therapies in the EM?IM?GG?GA?GA+AA groups,and the incidence of planned revascularization events was statistically difference in the GA+AA group.3.Logistic regression analysis showed that the age of the patients(P=0.024)and the number of vascular lesions(P<0.001)were risk factors for adverse cardiovascular events.4.A total of 262 IM patients were enrolled,of whom 228 were taking clopidogrel and 34 were taking ticagrelor.According to the follow-up results,there showed statistical differences in the incidence of all adverse cardiovascular events between the 6-month and the 12-month therapies in the clopidogrel group(P=0.004).There were no significant differences in the incidence of MACE?adverse cardiovascular events and hemorrhagic complications between the clopidogrel group and the ticagrelor group.Conclusion:After anti-platelet precision therapy in patients with ACS after PCI based on CYP2C19,there was no significant difference in the incidence of adverse cardiovascular events and bleeding events among different genotype groups,indicating better effecy and safety of precision medicine which reduces the incidence of risk events in traditional treatments.It was concerned that adverse cardiovascular events likely occured within six months after surgery.Although there was no statistically difference in the incidence of bleeding events,it was still necessary to pay attention to the occurrence of bleeding events during the anticoagulant therapy.
Keywords/Search Tags:acute coronary syndrome, percutaneous coronary intervention, gene polymorphism, clopidogrel, ticagrelor
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