细胞色素P450 2C19基因多态性对氯吡格雷抗血小板作用的影响  

Effect of cytochrome P450 2C19 gene polymorphism on clopidogrel antiplatelet therapy

作　　者：马辉[1] 吕慧怡[1] 于晓杰 胡增春[3] 孙丽晶[1] 程荔春[1] 张策[1] 

机构地区：[1]大连医科大学附属第二医院药学部,辽宁大连116027 [2]大连医科大学附属第一医院药剂科,辽宁大连116027 [3]大连医科大学附属第二医院神经外科,辽宁大连116027

出　　处：《中国临床药理学杂志》2017年第19期1909-1911,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究急性冠状动脉综合征患者行经皮冠状动脉介入治疗(PCI)后,细胞色素P450 2C19(CYP2C19)基因多态性对氯吡格雷抗血小板治疗的影响。方法纳入行PCI治疗的急性冠状动脉综合征患者55例(术后常规服用氯吡格雷和阿司匹林)、健康体检人群23例,用基因芯片法检测氯吡格雷药物代谢酶CYP2C19的基因型,利用流式细胞术检测患者术后2天外周血中血小板活化标记物可溶性P-选择素(CD62p)和血小板活化糖蛋白GPIIb/IIIa纤维蛋白原受体(PAC-1)的含量。根据统计学四分位数间距法计算CD62p、PAC-1的表达量。结果 55例患者中,7例为慢代谢组(CYP2C19*2/*2),28例为杂合中代谢组(CYP2C19*1/*2,CYP2C19*1/*3),20例为纯合快代谢组(CYP2C19*1/*1)。健康对照组,杂合中代谢*1/*2组,杂合中代谢1*/3*组和慢代谢*2/*2组CD62p的表达率分别为(6.73±5.69)%,(10.94±9.80)%,(14.35±6.24)%,(16.80±13.65)%;PAC-1的表达率分别为(1.06±0.69)%,(2.10±4.09)%,(2.37±3.15)%,(2.89±2.75)%,差异均有统计学意义(均P<0.05)。快代谢基因型的患者对氯吡格雷的反应性高,杂合中代谢的患者对氯吡格雷反应性呈中等水平,慢代谢患者对氯吡格雷的反应性低。结论杂合中代谢的患者对氯吡格雷反应性呈中等水平,建议增加氯吡格雷服药剂量或改用其他抗血小板药物治疗;慢代谢患者对氯吡格雷的反应性低,建议改用其他药物进行抗血小板治疗。Objective To investigate the effect of cytochrome P4502C19（ CYP2C19） gene polymorphism on the antiplatelet therapy of clopidogrel in patients who underwent percutaneous coronary intervention（ PCI）. Methods Fifty-five patients who underwent PCI,as well as twenty-three healthy subjects, were enrolled in this study. The genotypes of the samples were identified by gene chips hybridization. The contents of soluble P-selectin（ CD62p） and platelet glycoprotein GPⅡb/Ⅲa fibrinogen receptor（ PAC-1） in patients who underwent PCI were detected by flow cytometry（ FCM）. The expressions of platelet activation markers were calculated according to interquartile range method.Results Seven patients with CYP2C19 ＊ 2/＊ 2 genotypes were poor metabolizers,while twenty-eight patients with CYP2C19 ＊ 1/＊ 2,CYP2C19 ＊ 1/＊ 3 were intermediate metabolizers,twenty patients with CYP2C19＊ 1/＊ 1 were extensive metabolizers.In intermediate metabolism（ ＊ 1/＊ 2）,intermediate metabolism（ ＊ 1/＊ 3） and poor metabolism group,the CD62 p expressions were（ 6. 73 ± 5. 69） %,（ 10. 94 ± 9. 80） %,（ 14. 35 ± 6. 24） %,（ 16. 80 ± 13. 65） %,respectively,statistically significant differences were found when compared with the control group; The PAC-1 expressions were（ 1. 06 ± 0. 69） %,（ 2. 10 ± 4. 09） %,（ 2. 37 ± 3. 15） %,（ 2. 89 ± 2. 75） %,and there were significant differences in CD62 p and PAC-1 among the groups（ P〈0. 05）. The genotypes of extensive metabolism was high in the response to clopidogrel, while those of intermediate metabolism were moderate and poor metabolism were low.Conclusion Intermediate metabolism genotype patients could be adjusted to the dose of clopidogrel or the use of other antiplatelet drugs,and the poor metabolism genotype patients should be used other antiplatelet drugs.

关 键 词：基因多态性 氯吡格雷 经皮冠状动脉介入治疗 P-选择素 GPIIb/IIIa纤维蛋白原受体 

分 类 号：R973[医药卫生—药品]