CYP2C19、ABCB1和PON1基因多态性与氯吡格雷抑制血小板聚集作用的相关性研究

目的:探讨CYP2C19、ABCB1和PON1基因多态性与氯吡格雷抑制血小板聚集作用的相关性。方法:纳入诊断为急性缺血性脑卒中或接受经皮冠状动脉介入术(PCI)后服用氯吡格雷和阿司匹林治疗的患者59例,测定CYP2C19(rs4244285、rs4986893)、ABCB1(rs1045642)和PON1(rs662)基因型及血栓弹力图(TEG),并对患者进行1年的随访,记录临床终点事件。应用单因素和多因素回归,分析患者CYP2C19、ABCB1、PON1基因型、一般情况及临床因素对氯吡格雷抑制血小板聚集作用的影响,比较不同基因型患者的氯吡格雷疗效。结果:59例患者中氯吡格雷治疗相关的血小板高反应性(HTPR)的发生率为8.5%。CYP2C19快代谢型、中间代谢型和慢代谢型患者血小板抑制率分别为(86.0±10.1)%、(78.4±17.3)%和(66.4±23.0)%,快代谢型和慢代谢型之间血小板抑制率差异有显著性(P=0.047),ABCB1和PON1各基因型之间血小板抑制率的差异无显著性(P>0.05),全变量多因素logistic回归分析未发现CYP2C19、ABCB1、PON1基因型与HTPR相关(P=0.681)。随访1年中,CYP2C19快代谢型、中间代谢型、慢代谢型患者的临床事件分别有2、3和3例;ABCB1携带TT、TC、CC等位基因患者的临床事件分别有1,3和4例;PON1携带AA、AG、GG等位基因患者的临床事件分别有4,2和2例,各基因型之间患者临床终点事件差异无显著性(P>0.05)。结论:根据CYP2C19、ABCB1和PON1基因多态性尚不能预测服用氯吡格雷后的临床疗效。

Correlation between CYP2C19,ABCB1,PON1 gene polymorphism and clopidogrel antiplatelet aggregation reactivity

OBJECTIVE To study the relationship between CYP2C19, ABCB1, PON1 gene polymorphism and clopidogrel antiplatelet aggregation reactivity. METHODS In a total of 59 patients with acute ischemic stroke or post percutaneous coronary intervention treated with clopidogrel and aspirin, CYP2C19 (rs4244285, rs4986893), ABCB1 (rs1045642), PON1 (rs662) genotype and thrombelastogram (TEG) were detected. Clinical endpoint events were recorded after following up for 1 year after PCI after PCI and acute ischemic stroke. The effects of CYP2C19, ABCB1, PON1 genotype, demographic characteristics and clinical factors on clopidogrel antiplatelet aggregation reactivity were explored by univariate and multivariate logistic regression, and the clinical efficacy of clopidogrel in patients with different genotypes was compared. RESULTS The incidence of high on-clopidogrel treatment platelet reactivity (HTPR) was 8.5% in 59 patients. The platelet inhibition rates in patients of the extensive metabolic type, intermediate metabolic type and poor metabolic type of CYP2C19 were (86.0±10.1)%, (78.4±17.3)% and (66.4±23.0)%, respectively. There was significant difference in the platelet inhibition rates between extensive metabolizers and poor metabolizers (P=0.047), and no significant difference between genotypes of ABCB1 and PON1 (P>0.05). Multi-factor logistic regression showed no relationship between CYP2C19,ABCB1,PON1 genotype and HTPR (P=0.681). After follow-up for 1 year, the clinical endpoint events of extensive metabolizers, intermediate metabolizers and poor metabolizers were 2, 3 and 3 cases, respectively. The clinical endpoint events of ABCB1 in patients carried TT, TC, and CC allele were 1, 3 and 4 cases, respectively. The clinical endpoint events of PON1 in patients carried AA, AG and GG allele were 4, 2 and 2 cases, respectively. There were no significant difference in the clinical endpoint events among CYP2C19,ABCB1 and PON1 genotype (P>0.05). CONCLUSION The clinical efficacy of clopidogrel cannot be predicted according to the CYP2C19,ABCB1,PON1 polymorphism.