PCI术后患者PON1-126C>G基因多态性对氯吡格雷所致出血事件的影响研究

The influence of PON1-126C>G gene polymorphisms on bleeding events caused by clopidogrel in patients after PCI

目的:研究PCI术后患者PON1-126C>G基因多态性对氯吡格雷抗血小板治疗后出血事件的影响。方法:研究对象选自2014年6月至2015年9月,在某院心内科住院行PCI术的患者,所有患者均接受标准双联抗血小板治疗。收集全血,提取DNA,采用Sequenom MassARRAY基因分型技术进行PON1-126C>G、CYP2C19*17基因型分析;采用HPLC-UV法测定羧酸氯吡格雷代谢物(CLPM)血药浓度;采用PL^(-1)1血小板分析仪检测血小板聚集功能;随访患者PCI术后12个月内的出血事件。结果:共纳入384例患者,依据随访结果,分为出血组与非出血组,PON1-126G突变型即CG+GG基因型分布频率在2组之间的差异具有显著性(28.57%vs.13.47%,χ~2=4.712,P=0.046);CYP2C19*17突变型即CT基因型分布频率在两组之间的差异也具有显著性(10.71%vs.2.30%,χ~2=6.462,P=0.041)。结论:PON1-126CG+GG基因型与PCI术后12个月内氯吡格雷所致出血事件发生显著相关,该基因型检测可有效预测出具有出血风险的高危患者,从而调整氯吡格雷给药方案,改善预后。

OBJECTIVE To investigate the effect of PONl-126C〉G genetic polymorphisms on bleeding events caused by clopidogrel in patients after percntaneous coronary intervention （PCI）. METHODS The subjects were treated with standard dual antiplatelet therapy after PCI in the cardiology department of a tertiary A hospital from June 2014 to September 2015. Genotyping of PONI-126C〉G and CYP2C19＊ 17 was performed by Sequenom MassARRAY platform. The blood concentration of clopidogrel carboxylic acid metabolites （CLPM） was detected by high performance liquid chromatography with ultraviolet detector and the platelet aggregative function by PL-11 analyzer. The patients＇ bleeding events were observed during follow- up within 12 months after PCI. RESULTS A total of 384 patients were sequentially enrolled, divided into two groups （bleeding group and non bleeding group） according to the follow up results. The genotype frequencies of PON1 126G carriers （CG ＋ GG） were significantly different among two groups （28. 57% vs. 13.47% ,χ^2 = 4.712, P = 0.046）. It was the same with CYP2C19＊ 17 mutations （10. 71% vs. 2. 30%, ）χ^2 = 6. 462, P = 0. 041）. CONCLUSION PON1-126 CG＋ GG genotypes might be significantly related with bleeding events caused by clopidogrel 12 months after PCI. The genotyping of PON126C〉G will be effective in predicting the risk of bleeding. In this light, the antiplatelet therapy of clopidogrel can be adjusted to improve the patient prognosis.