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

发布时间：2018-11-08 18:41

【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P0.05)。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。
[Abstract]:Objective to study the effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism on clopidogrel antiplatelet therapy after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). Methods 55 patients with acute coronary syndrome treated with PCI (routine clopidogrel and aspirin) and 23 healthy controls were enrolled. The genotypes of clopidogrel drug metabolizing enzyme CYP2C19 were detected by gene chip method. The contents of soluble P- selectin (CD62p) and platelet activated glycoprotein (GPIIb/IIIa) fibrinogen receptor (PAC-1) in peripheral blood of patients 2 days after operation were detected by flow cytometry. The expression of CD62p,PAC-1 was calculated by statistical quartile spacing method. Results among 55 patients, 7 were slow metabolic group (CYP2C19*2/*2), 28 were heterozygous metabolic group (CYP2C19*1/*2,CYP2C19*1/*3) and 20 were homozygous fast metabolism group (CYP2C19*1/*1). The expression rates of CD62p were (6.73 卤5.69)%, (10.94 卤9.80)%, (14.35 卤6.24)%, respectively in the healthy control group, the heterozygous metabolism 1 / 1 / 2 group, the heterozygous metabolism 1 / 1 / 3 * group and the slow metabolism * 2 / 2 group, respectively. (16.80 卤13.65)%; The expression rates of PAC-1 were (1.06 卤0.69)%, (2.10 卤4.09)%, (2.37 卤3.15)%, (2.89 卤2.75)%, respectively (P0.05). The patients with fast metabolic genotype had high reactivity to clopidogrel, the patients with heterozygosity showed moderate reactivity to clopidogrel, and the patients with slow metabolism had low reactivity to clopidogrel. Conclusion the reactivity to clopidogrel was moderate in patients with heterozygous metabolism. It was suggested that the dosage of clopidogrel should be increased or other antiplatelet drugs should be used. Patients with slow metabolism are less reactive to clopidogrel, and other drugs are recommended for antiplatelet therapy.
【作者单位】：大连医科大学附属第二医院药学部;大连医科大学附属第一医院药剂科;大连医科大学附属第二医院神经外科;
【分类号】：R541.4

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