细胞色素P450 2C19*2基因多态性联合钙通道阻滞剂与冠状动脉支架内血栓形成的相关性

Relationship between Cytochrome P450 2C19*2 polymorphism unite calcium-channel blockers and stent thrombosis in patients undergoing percutaneous coronary intervention

目的:探讨经皮冠状动脉介入术(PCI)后接受氯吡格雷治疗的患者中,细胞色素P450 2C19(CYP2C19)*2基因多态性(681A)与支架内血栓形成的相关性,以及服用钙通道阻滞剂(CCBs)与支架内血栓形成的相关性。方法:检测1 738例冠心病PCI术后患者的CYP2C19基因多态性,并将这些患者分为CCBs组和非CCBs组,采用比浊法检测二磷酸腺苷(ADP)途径诱导的血小板最大聚集率(MPAR),比较两组患者MPAR及支架内血栓形成率的差异。结果:19例(2.4%)CYP2C19*2基因型的患者(包括CYP2C19*2/*2或*1/*2)和7例(0.75%)基因型为CYP2C19*1/*1的患者发生了明确的支架内血栓形成;CYP2C19*2基因型患者支架内血栓形成的发生率明显高于CYP2C19野生型纯合子患者(CYP2C19*1/*1)(风险比为4.26,95%可信区间为1.28～9.22,P<0.05);基因型为CYP2C19*1/*1的患者发生支架内血栓形成的风险最低,而基因型为CYP2C19*2/*2的患者支架内血栓形成的风险最高(风险比为0.568,95%可信区间为0.308～2.070,P<0.01);CCBs组和非CCBs组MPAR及支架内血栓形成率差异无统计学意义。结论:PCI术后接受氯吡格雷治疗的冠心病患者中,CYP2C19*2基因型患者支架内血栓形成的风险增加,而服用CCBs不会导致氯吡格雷抗血小板聚集作用减弱以及支架内血栓形成事件增加。

Objective：To investigate the relationship between cytochrome P450 2C19（CYP2C19）＊2 polymorphism（681A） unite calcium-channel blockers（CCBs） and definite stent thrombosis（ST） in patients undergoing percutaneous coronary intervention（PCI）. Method： All 1 738 patients’ CYP2C19＊2 polymorphism status has been examined.The patients were divided into CCBs group and non CCBs group.Turbidimetry method was used to examine the maximal platelet aggregation rate induced by ADP in order to observe the anti-platelet aggregation effect of clopidogrel in the 2 groups. Result：The presence of at least one CYP2C19＊2 allele was significantly associated with increased ST risk [19 CYP2C19＊2/＊2 or ＊1/＊2 patients（2.4%） vs seven homozygous wild-type CYP2C19＊1/＊1 patients（0.75%,HR 4.26,95%CI 1.28-9.22,P〈0.01].The risk of ST was lowest in homozygous wild-type CYP2C19 patients and highest in patients carrying 2 mutant CYP2C19 alletes（＊2/＊2 genotype）,（3.1%,HR 0.568,95%CI 0.308-2.070,P〈0.01）.Statistical significance of MPAR was not observed between CCBs group and non CCBs group [（48.50±11.38）% vs（45.60±13.62）%,P〉0.05）].The incidence of ST was almost similar between 2 groups（1.51% vs 1.44%）. Conclusion：The CYP2C19＊2 genotype is associated with an increased risk of definite ST in patients undergoing PCI.CCBs would not decrease the anti-platelet aggregation effect of clopidogrel by laboratory tests,and didn’t increase the risk of definite ST in patients undergoing PCI.