| 摘要: |
| 目的 研究血栓弹力图对细胞色素 P450系统药物代谢酶CYP2C19基因型的预测作用及对经皮冠状动脉介入术(PCI)后氯吡格雷治疗的指导价值。 方法 选择2012年1月至 2012年8月于我科行PCI治疗的冠心病患者70例,均给予阿司匹林和氯吡格雷双联抗血小板药物治疗。根据对二磷酸腺苷(ADP)诱导的血小板聚集抑制率的测定结果分为氯吡格雷抵抗组和氯吡格雷敏感组。检测70例患者CYP2C19的基因型；根据不同等位基因功能缺失,分为快代谢基因型(*1/*1) 、中间代谢基因型(*1/*2,*1/*3)和慢代谢基因型(*2/*2,*2/*3,*3/*3)。比较氯吡格雷抵抗组和氯吡格雷敏感组患者的一般临床资料、生化指标和CYP2C19基因型的差异,多因素logistic回归分析氯吡格雷抵抗的危险因素。利用受试者工作曲线(ROC)检验血小板聚集抑制率预测CYP2C19基因型的效力。 结果 氯吡格雷抵抗组(31例)和氯吡格雷敏感组(39例)高密度脂蛋白水平、CYP2C19基因型的差异均有统计学意义(P<0.05)。逐步向前logistic回归分析结果显示CYP2C19慢代谢基因型和高密度脂蛋白水平降低为氯吡格雷抵抗的独立危险因素(P<0.05)。利用血小板聚集抑制率预测CYP2C19基因型的ROC曲线下面积(AUC)为0.847(95% CI: 0.729～0.965,P=0.003),提示效力较好;当血小板聚集抑制率取最佳临界值 (39.45%)时,诊断CYP2C19基因型为慢代谢型的敏感性为85.7%,特异性为77.8%,阳性预测值为30%,阴性预测值为98%。 结论 携带CPY2C19慢代谢基因型和高密度脂蛋白水平降低是导致氯吡格雷抵抗的独立危险因素。当血小板聚集抑制率小于39.45%时,应对患者做CYP2C19基因型的检测,以调整治疗方案。 |
| 关键词: 血栓弹力图 氯吡格雷 CYP2C19 经皮冠状动脉介入术 |
| DOI： |
| 投稿时间：2013-03-11修订日期：2013-06-06 |
| 基金项目: |
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| Value of CYP2C19 genotype predicted by thromboelastography in guiding clopidogrel treatment following percutaneous coronary intervention |
| DONG Jin-kun,MENG Shu*,CHEN Jun-wen,SUN Ying-gang,SHEN Cheng-xing |
(Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
*Corresponding author.) |
| Abstract: |
| Objective To investigate the role of thromboelastography (TEG) in predicting cytochrome P450 2C19 (CYP2C19) genotype and its value in guiding clopidogrel treatment following percutaneous coronary intervention (PCI). Methods From January 2012 to August 2012, 70 patients with coronary artery disease undergoing PCI were enrolled and treated with aspirin and clopidogrel. They were divided into clopidogrel resistance (CR) group and clopidogrel sensitive (CS) group according to adenosine diphosphate (ADP)-induced platelet aggregation inhibition rate. Genotyping of CYP2C19 in the 70 patients was classified as: extensive metabolizers(*1/*1), intermediate metabolizers(*1/*2, *1/*3) and poor metabolizers(*2/*2, *2/*3, *3/*3). The clinical data, biochemical parameters, and CYP2C19 genotypes were compared between two groups. The independent risk factors of CR were analyzed by multiple logistic regression analysis. A receiver operating characteristic (ROC) curve was used to evaluate the efficacy of ADP-induced platelet aggregation inhibition rate in predicting the genotype of CYP2C19. Results High-density lipoprotein and genotypes of CYP2C19 were significantly different between the CR group (n=31) and CS group (n=39)(P<0.05). Stepwise forward multiple logistic regression analysis found that CYP2C19 poor metabolizers and lower HDL level were independent risk factors for CR (P<0.05). The results of ROC curve demonstrated a satisfactory predictive value for ADP-induced platelet aggregation inhibition rate, with the area under the curve (AUC) being 0.847 (95% CI: 0.729-0.965,P=0.003). When the ADP-induced platelet aggregation inhibition rate was at the optimal cut-off value (39.45%), the sensitivity, specificity, positive predictive value and negative predictive value in diagnosing the poor metabolizers of CYP2C19 were 85.7%, 77.8%, 30% and 98%, respectively. Conclusion CYP2C19 poor metabolizers and lower HDL level are selected as the independent risk factors of CR. When the ADP-induced platelet aggregation inhibition rate is lower than 39.45%, the genotypes of CYP2C19 should be detected to adjust the treatment. |
| Key words: thromboelastography clopidogrel CYP2C19 percutaneous coronary intervention |
