P2Y12 基因启动子 DNA 甲基化与冠心病患者氯吡格雷抵抗风险的关联。
Association of P2Y12 gene promoter DNA methylation with the risk of clopidogrel resistance in coronary artery disease patients.
机构信息
Department of Cardiology, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, China.
Department of Traditional Chinese Internal Medicine, The Affiliated Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
出版信息
Biomed Res Int. 2014;2014:450814. doi: 10.1155/2014/450814. Epub 2014 Mar 18.
BACKGROUND
Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet aggregation. The goal of our study is to investigate the contribution of P2Y12 promoter DNA methylation to the risk of clopidogrel resistance (CR).
METHODS
The platelet functions were measured by the VerifyNow P2Y12 assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among P2Y12 DNA methylation, various biochemical characteristics, and CR.
RESULT
Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1, P=0.009; CpG2, P=0.022) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients (P=0.026) and in subgroup of Albumin<35 (P=0.002). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR.
CONCLUSIONS
The evidence from our study indicates that P2Y12 methylation may bring new hints to elaborate the pathogenesis of CR.
背景
氯吡格雷通过抑制 ADP 受体 P2Y12 来抑制血小板聚集。本研究旨在探讨 P2Y12 启动子 DNA 甲基化在氯吡格雷抵抗（CR）风险中的作用。
方法
采用 VerifyNow P2Y12 检测血小板功能，应用亚硫酸氢盐焦磷酸测序技术检测 P2Y12 启动子两个 CpG 二核苷酸的 DNA 甲基化水平，比较 49 例 CR 病例和 57 例非 CR 对照之间的差异。同时还探讨了 P2Y12 DNA 甲基化与各种生化特征和 CR 的关系。
结果
在酗酒状态下，两个 CpG 位点的低甲基化预示着氯吡格雷反应较差（CpG1，P=0.009；CpG2，P=0.022）。同时，在吸烟患者（P=0.026）和白蛋白<35 的亚组中，CpG1 甲基化与 CR 呈负相关（P=0.002）。我们观察到 DNA 甲基化水平可能受到一些临床标志物的影响，如 TBIL、LEVF、白蛋白、AST。研究结果还表明，支架数量、空腹血糖和较低的 HbAC1 是 CR 的预测因素。
结论
本研究结果表明，P2Y12 甲基化可能为阐明 CR 的发病机制提供新的线索。
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