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Research Of The Correlation Between The Promoter Methylation Of The ABCB1 Gene And Clopidogrel Pharmacodynamics In Han Chinese

Posted on:2016-09-20Degree:MasterType:Thesis
Country:ChinaCandidate:J Y ZhongFull Text:PDF
GTID:2284330476952094Subject:Internal Medicine
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Objective: To explore the influences of the ABCB1 gene methylation level on clopidogrel pharmacodynamics in patients with ST-segment elevation myocardial infarction(STEMI) under percutaneous coronary intervention(PCI).Methods: A total of 14 patients with ST-segment elevation myocardial infarction(STEMI) under percutaneous coronary intervention(PCI) during June 2013 to March 2014 in Ningbo First Hospital was enroll in the research. All patients were treated by clopidogrel(300mg) and aspirin(300mg), and were collected blood samples at 1, 2, 4, 8 and 24 h after administration. Obtaining the result of residual platelet activity unit by using VerifyNow-P2Y12 to estimate the function of platelet. Meanwhile, the DNA methylation levels of the CpG island region on the ABCB1 gene was measured through the sodium bisulfite DNA conversion and pyrosequencing technology. The date was analyzed by SPSS 16.0 software.Results: Neither residual platelet activity unit nor platelet inhibition rate was no significant associated with ABCB1 gene promoter DNA methylation in this trial(P = 0.820.P = 0.966).There was a positive significant association between ABCB1 gene promoter DNA methylation and platelet inhibition rate at 4h after administration(r = 0.587,P = 0.027). ABCB1 promoter methylation was negatively associated with platelet inhibition rate at 8h after administration(r =-0.534,P = 0.049). Two samples of promoter methylation were positively associated with residual platelet activity unit(r = 0.904 P = 0.035, r = 0.976 P = 0.004).Conclusions: There is no unified theory to explain the complicated mechanism of clopidogrel pharmacodynamics. So far, One of the most rapid detection methods is VerifyNow-P2Y12 which is designed to detect the residual platelet activity unit. ABCB1 promoter methylation was associated with pharmacodynamics of clopidogrel. However, not all of ABCB1 gene methylation levels was associated with clopidogrel pharmacodynamics.
Keywords/Search Tags:Clopidogrel, pharmacodynamics, ABCB1, gene promoter DNA methylation
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