中国汉族人群ABCB1基因启动子甲基化与氯吡格雷药效动力学的关联研究

发布时间：2019-03-15 17:20

【摘要】：目的:探讨ABCB1基因甲基化水平对ST段抬高性心肌梗死患者经皮冠状动脉介入治疗术后患者氯吡格雷药效动力学的影响。方法:收入2013年6月至2014年3月期间在宁波市第一医院住院并行介入治疗的ST段抬高性心肌梗死患者共14例。所有患者给予氯吡格雷300mg及阿司匹林300mg治疗,并分别在服药后的1小时、2小时、4小时、8小时及24小时进行静脉采血。运用Verify Now-P2Y12法进行血小板功能的评估,得到剩余血小板活性单位。同时以焦磷酸测序方法对ABCB1基因的Cp G岛进行DNA甲基化检测。采用SPSS 16.0软件对数据进行分析。结果:总体ABCB1基因甲基化水平与剩余血小板活性单位在这个实验中并没有发现具有显著的相关性(P=0.820),与血小板抑制率也没有显著的相关性(P=0.966)。在服药后的4小时ABCB1基因甲基化水平与血小板抑制率具有显著的正相关性(r=0.587,P=0.027)。8小时的ABCB1基因甲基化水平与血小板抑制率则具有负相关性(r=-0.534,P=0.049)。两个样本的甲基化水平与剩余血小板活性单位具有正相关性(r=0.904 P=0.035,r=0.976 P=0.004)。结论:氯吡格雷药效学的机制十分复杂,尚无统一的理论对这一机制进行解释。目前,Verify Now-P2Y12法可能是针对氯吡格雷的特定抑制途径对剩余血小板活性单位进行检测的最快速的检测手段之一。ABCB1基因甲基化水平与氯吡格雷的药效学存在相关性。然而,并不是每个个体的ABCB1基因甲基化水平均与氯吡格雷的药效学相关。
[Abstract]:Aim: to investigate the effect of methylation level of ABCB1 gene on the pharmacodynamics of clopidogrel in patients with ST segment elevation myocardial infarction after percutaneous coronary intervention (PCI). Methods: from June 2013 to March 2014, 14 patients with ST segment elevation myocardial infarction were admitted to Ningbo first Hospital and treated with interventional therapy. All patients were treated with clopidogrel 300mg and aspirin 300mg. Venous blood samples were collected at 1 hour, 2 hours, 4 hours, 8 hours and 24 hours respectively. Verify Now-P2Y12 method was used to evaluate platelet function and the remaining platelet activity units were obtained. At the same time, the DNA methylation of Cp G island of ABCB1 gene was detected by pyrophosphoric acid sequencing. The data were analyzed by SPSS 16.0 software. Results: there was no significant correlation between the methylation level of the total ABCB1 gene and the residual platelet activity unit in this experiment (P < 0. 820), nor was there a significant correlation between the methylation level of the total DNA gene and the platelet inhibition rate (P < 0. 966). There was a significant positive correlation between the methylation level of ABCB1 gene and platelet inhibition rate at 4 hours after treatment (r = 0.587, P < 0.027), and a negative correlation between methylation level of ABCB1 gene at 8 hours and platelet inhibition rate (r = 0.534, P < 0.05, P < 0.01). (P = 0.049). There was a positive correlation between the methylation level of the two samples and the residual platelet activity units (r = 0.904 P = 0.035, r = 0.976 P = 0.004). Conclusion: the mechanism of clopidogrel pharmacodynamics is very complex and there is no unified theory to explain this mechanism. At present, Verify Now-P2Y12 may be one of the most rapid methods for detecting residual platelet active units through a specific inhibition pathway of clopidogrel. There is a correlation between the methylation level of ABCB1 gene and the pharmacodynamics of clopidogrel. However, not every individual's ABCB1 gene methylation level is associated with clopidogrel's pharmacodynamics.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R542.22

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