CYP2C19基因多态性与氯吡格雷抗凝作用的相关性研究

Correlation study of gene polymorphism of CYP2C19 and anticoagulation effect of clopidogrel

目的:探讨细胞色素P450(CYP)2C19基因多态性与氯吡格雷抗凝作用的关系,为氯吡格雷个体化用药提供参考。方法:选取诊断为急性冠脉综合征并接受经皮冠状动脉介入治疗术(PCI)的患者,采取血标本并提取外周血基因组DNA,将提取后的总DNA进行PCR扩增,扩增产物经基因芯片杂交法确定基因型,根据不同的基因型对患者进行分组。176例入选病例共分为3组,A组:快代谢基因组(CYP2C19*1/*1);B组:中等代谢基因组(CYP2C19*1/*2、CYP2C19*1/*3);C组:慢代谢基因组(CYP2C19*2/*2、CYP2C19*2/*3或CYP2C19*3/*3),测定各组ADP抑制率。应用SPSS 13.0软件对数据进行统计分析。结果:176例入选病例三组之间ADP抑制率差异无统计学意义(P>0.05),127例首次行PCI患者中C组与B组和A组相比,ADP抑制率差异有统计学意义(P<0.05和P<0.01)。结论:首次经皮冠状动脉介入治疗术后CYP2C19慢代谢基因型患者常规使用氯吡格雷疗效较差。

Objective： To explore the correlation between the gene polymorphism of CYP2C19 and anticoagulation effect of clopidogrel, and provide the reference for individualized medication of clopidogrel. Methods： The peripheral bloods of 176 post- PCI patients who were diagnosed with acute coronary syndromes were drawn, genomic DNAs were extracted and amplified by PCR, and then the genotypes of those samples were identified by gene chips hybridization. The subjects were divided into three groups by genotype. Group A consisted of patients with the genotype of extensive metabolism （CYP2C 19＊ 1/＊ 1）, group B consisted of patients with the genotype of intermediated metabolism （CYP2C19＊ 1/＇2 and CYP2C19＊ 1/＇3）, and group C consisted of patients with the genotype of poor metabolism （CYP2C19＊2/＇2, CYP2C19＊2/＇3 and CYP2C19＊3/＇3）. The ADP inhibition rates in different groups were evaluated. The data were analyzed by SPSS 13.0 software. Results： There were no significant differences of ADP inhibition rate among the three groups （P 〉 0.05）, but when compared to group B and group A, the ADP inhibition rates in group C were significantly lower in 127 patients with first PCI （P 〈 0.05 and P 〈 0.01）. Conclusion： The anticoagulant effect of clopidogrel in the CYP2C 19 poor metabolism genotype patients with first PCI was poor.