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Clinical Significance CYP2C19,ABCB1 Gene In Patients With Acute Cononary Syndrome

Posted on:2016-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:T YeFull Text:PDF
GTID:2284330470482441Subject:Internal medicine
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Objective:To explore the determination of clopidogrel in patients with acute coronary syndrome(ACS) on the metabolic pathways related genes CYP2C19,ABCB1 clinical significance.Methods:Select from 100 patients in our Hospital of Geriatrics and cardiovasculars hospitalized with acute coronary syndrome in July 2013 to May 2014, taking 5ml peripheral blood of patients sent to hospital pharmacy line Yijishan clopidogrel-related gene CYP2C12, ABCB1 testing drugs before taking clopidogrel after peripheral blood using optical turbidity measurement is calculated The maximum rate of platelet aggregation. In treatment, give patients with clopidogrel and aspirin antiplatelet, its dose was 75 mg and 100 mg. In the above treatment after 24 h and dual anti-law again after five days of treatment for patients with platelet aggregation rate testing.Placement in the treatment of patients undergoing coronary angiography bracket, if the patient has a continuous line of six days of aspirin and clopidogrel 75 mg 100mg double-antibody therapy, continue to be taken before the surgery doses above; if less than six days before the surgery to be load antiplatelet therapy with aspirin 300 mg and 300 mg clopidogrel.When platelet aggregation rate is less than or equal to 10%, it is called clopidogrel resistance(CR), if the result is greater than 10% is called clopidogrel non-resistance(NCR). The results need to be analyzed by the SPSS statistical software, comparing patients with different genotypes carrying the probability of their occurrence clopidogrel resistance, analyze whether the correlation between the two. For patients undergoing PCI, after the discharge, the law taking clopidogrel 75 mg treatment for at least a year, and these patients were followed up laws 1,3,6 months. Bank of PCI, 100 patients of 25 patients with major cardiovascular events(MACE). Application Logsitic regression analysis of clinical data to assess the impact on the various genotypes of MACE.Results:1)Gene distribution: 100 patients, CYP2C19 gene into wild-type(G / G), homozygote(A / A), heterozygous(G / A) into three types, which CYP2C19 * 2, respectively, the proportion of the three genotypes is: 48%, 14%, 38%. * 3 percentage of the three genotypes were 95%, 3%, 2%. Furthermore CYP2C19 gene polymorphism can also be divided into three metabolic type, namely fast, slow, three kinds, the proportion of 100 patients were 46%, 36%, 18%; ABCB1 gene into wild-type CC mutant CT and TT type three, the proportion was 35%, 44%, 31%.2)100 patients were measured before taking clopidogrel platelet aggregation rate distribution 24.65%-70.35%, with an average of(40.43 ± 10.78), taking 75 mg clopidogrel 24 hours a measured distribution MPA 4.87%-59.02%, with an average of(23.52 ± 11.35)%, the results obtained in 100 patients appear CR 21 cases, NCR has a 79% probability of CR was 21%. Five days later excluded 25 patients underwent PCI surgery, measured enrolled 75 patients taking the drug before the distribution of MPA in the range of 26.55%-68.79 average of(39.44 ± 9.56)%, after taking MPA distributed in 2.63%-53.48%, With an average of(20.37 ± 9.32)%. Platelet decline of 1.96%-53.57%, an average of(18.56 ± 14.13)%. May appear in CR 75 patients, 24 cases, 51 cases occurred in patients with no resistance, the probability of the occurrence of CR events by up to 32 percent of patients with the results obtained by. 100 patients with clinical data, laboratory examination, history-related diseases and drug history taking and if no significant correlation between the occurrence of CR.3)The correlation between Gene polymorphism and CR: CYP2C19 * 2 is divided into three metabolic type, which occurs in the CR rates were 14.2%, 21.1%, 46.2%. Three metabolic type distribution in CR group had statistically significant(P <0.05). * 3 gene three metabolites in the CR type occurrence ratio of 20%, 0.0%, 66%. Three metabolic type distribution statistically significant(P <0.05) in the CR group. Three gene ABCB1 genotype distribution in the CR ratio of 23.3%, 45.9%, 30.9%, of which TT genotype distribution in the presence of CR and NCR two statistical significance(P = 0.001). CYP2C1 P three metabolic type occur in the CR ratios were 4.3%, 27.7%, 44.4%, three metabotropic statistically significant(P <0.05) in the CR distribution.4)CR risk factors: the regression analysis by Logsitic CYP * 2 and ABCB1 gene and whether there is correlation between the occurrence of CR(OR7.78, 95% CI1.79-33.68, P0.007; OR1.68, 95% CI1.24-2.12, P0.02).5)MACE risk factors: CYP2C19 metabolizers A group of wild-type, mutant for group B, the distribution ratio: 44%, 56%. MACE occurred two ratios were 9.1%, 28.3%, the result in statistically significant(P <0.05). ABCB1 three metabolic type distribution was 36%, 44%, 20%. Wild-type for the group C, group D mutant, the occurrence of MACE compared the two groups were 11.1%, 18.8%, showed no significant difference(P> 0.05). Logistic regression analysis, carry the gene CYP2C19 LOF for MACE risk factors(OR 2.8,95% CI 1.31-6.08 P 0.009).Conclusions: Acute coronary syndrome patients of Han population in Wannan region, CYP2C19 and ABCB1 gene polymorphisms may be correlated with clopidogrel resistance.CYP2C19 * 2 genotype may be risk for the clopidogrel resistance. The occurrence of major adverse cardiovascular events with clopidogrel metabolism correlated.
Keywords/Search Tags:Acute coronary syndrome, Antiplatelet therapy, Clopidogrel and Clopidogre Resistance, ABCB1 and CYP2C19 gene polymorphism
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