CYP2C19基因多态性与颈动脉支架植入术后氯吡格雷治疗预后的关联研究

Relationship between CYP2C19 gene polymorphism and outcome of Clopidogrel therapy after carotid artery stenting

目的 探讨CYP2C19基因多态性与颈动脉支架植入术后长期采用氯吡格雷抗血小板治疗缺血性卒中复发风险之间的相关性.方法 选择2014年1月至2018年1月在广州市第一人民医院神经内科颈动脉支架术后的颈动脉狭窄患者83例,采用DNA微阵列芯片法检测CYP2C19基因多态性,术后采用阿司匹林(100 mg/d)及氯吡格雷(75 mg/d)抗血小板治疗6个月,双联抗血小板治疗后采用氯吡格雷(75 mg/d)长期抗血小板治疗,随访患者缺血性卒中复发情况,分析CYP2C19基因多态性与颈动脉支架术后氯吡格雷治疗缺血性卒中复发的关系.结果 平均随访26个月(12~36月),20例颈动脉支架术后患者发生缺血性卒中,快代谢型3例,中代谢型发生缺血性卒中12例,慢代谢型发生缺血性卒中5例;中代谢型、慢代谢型患者的卒中发生风险高于快代谢型患者(OR=4.92,95% CI :1.26~19.31, P=0.015,OR=10.67,95%CI :1.92~59.2,P=0.008).发现CYP2C19功能缺失(LOF)携带数与脑卒中发生存在相关(P=0.002),携带有1个LOF等位基因者脑卒中复发的风险是未携带者的3.21倍(95% CI :1.23~9.05,P<0.05),携带2个LOF等位基因者脑卒中复发的风险时未携带者的10.21倍(95% CI :2.62~40.24,P<0.05).结论 颈动脉支架植入术后长期采用氯吡格雷抗血小板治疗的患者,中慢代谢型患者的卒中复发风险较快代谢型升高.LOF携带数与颈动脉支架植入术后脑卒中发生存在相关.

Objective To investigate the relationship between CYP2C19 gene polymorphism and the risk of ischemic stroke recurrence with long?term Clopidogrel antiplatelet therapy after carotid artery stenting.Methods Eighty?three patients with carotid stenosis,who underwent carotid artery stenting in the Department of Neurology,Guangzhou First Municipal People’s Hospital between January 2014 and January 2018,were included in the study.The CYP2C19 gene polymorphism was determined by DNA microarray chip method.Aspirin(100 mg/d)and Clopidogrel(75 mg/d)were used for 6 months of antiplatelet therapy after the procedure.After dual antiplatelet therapy,Clopidogrel(75 mg/d)was used for long?term antiplatelet therapy,and the recurrence of ischemic stroke was followed up.The relationship between CYP2C19 gene polymorphism and the risk of ischemic stroke recurrence with long?term Clopidogrel antiplatelet therapy after carotid artery stenting was determined.Results After an average follow?up of 26 months(12?36 months),20 patients developed ischemic stroke after carotid artery stenting,including 3 rapid metabolizers,12 mild metabolizers,and 5 slow metabolizers.The risk of stroke in mild and slow metabolizers was higher than that in rapid metabolizers(OR=4.92,95%CI:1.26?19.31,P=0.015,OR=10.67,95%CI:1.92?59.2,P=0.008).The number of CYP2C19 loss of function(LOF)was associated with the stroke occurrence(P=0.002).The risk of stroke recurrence in patients with 1 LOF allele was 3.21 times higher than that in non?carriers(95%CI:1.23?9.05,P<0.05).The risk of stroke recurrence in patients with 2 LOF alleles was 10.21 times higher than that in non?carriers(95%CI:2.62?40.24,P<0.05).Conclusion In patients treated with long?term Clopidogrel antiplatelet therapy after carotid artery stenting,mild and slow metabolizers have higher risk of stroke recurrence compared with rapid metabolizers.The number of LOF carriers is associated with the occurrence of stroke after carotid artery stenting.