依据CYP2C19基因型调整首次PCI术后患者氯吡格雷给药剂量初步研究

摘要

Objective To explore the relation between the gentice polymorphism of CYP2C19 and clopidro-gel resistance so as to guide the clinical optimal antiplatelet therapy. Methods Genomic DNA was extracted from human blood cells of 127 cases after percutaneous coronary intervention (PCI). The alleles polymorphism of CYP2C19 *2 and CYP2C19 * 3 was detected by PCR.and direct PCR sequencing was used to detect the CYP2C19 genotype. Platelet reactivity was evaluated by thromboelastography (TEG). Difference between the groups was compared by SPSS 13.0 statistics software using ANOVA and LSD test. P <0. 05 was selected as the significant standard. Results The frequency of CYP2C19 * 1/ * 1 in these 127 patients was 41.7%. There were 45 patients with * 1/ * 2(35.4% ), 15 patients with * 1/ * 3 ( 11. 8% ) , 7 patients with * 2/ * 2 (5.5%), 7 patients with * 2/ * 3 (5. 5% ) and no patients with * 3/ * 3(0. 0% ) genotype. According to the genotypes of CYP2C19 ,these patients were divided into three groups;group A (CYP2C19 * 1/ * 1) , group B (CYP2C19 * 1/ * 2 or CYP2C19 * 1/ * 3) ,and group C ( CYP2C19 * 2/ * 2, CYP2C19 * 2/ * 3 , or CYP2C19 * 3/ * 3). The mean value of the ADP inhibition rate among the patients in group A and B was higher than that in group C, with statistical significance ( P < 0.05). Conclusion The genetic polymorphism of CYP2C19 affects the ADP inhibition rate, so the dosage of clo-pidrogel for patients with CYP2C19 * 2/ * 2, CYP2C19 * 2/ * 3 or CYP2C19 * 3/ * 3 allele should give a triple antiplatelet therapy after PCI.%目的 本研究旨在探讨CYP2C19基因多态性与二磷酸腺苷(ADP)抑制率之间的关系,以期能够早期预测氯吡格雷抵抗,为氯吡格雷的个体化用药提供参考依据.方法 选取127例诊断为急性冠脉综合症并首次接受经皮冠状动脉介入治疗术(PCI)的患者为研究对象,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,扩增产物经纯化后进行双向测序确定基因型,根据不同的基因型对患者进行分组；使用血栓弹力图测定ADP诱导的血小板聚集抑制率；多组均数间比较采用方差分析,多组均数间两两比较采用LSD-t检验,所有数据应用SPSS 13.0软件进行统计学处理.结果 127例患者中各基因型所占比例:CYP2C19* 1/*1为41.7％,CYP2C19* 1/*2为35.4％,CYP2C19*1/*3为11.8％,CYP2C19* 2/*2为5.5％,CYP2C19*2/*3为5.5％,CYP2C19* 3/*3为0％.携带正常基因纯合子(CYP2C19 * 1/* 1)的A组患者与携带有正常基因与突变基因杂合子(CYP2C19* 1/*2或CYP2C19* 1/*3)的B组患者ADP抑制率并无显著性差异,携带突变基因纯合子或杂合子的C组患者与B组和A组均有显著性差异(P ＜0.05和P＜0.01).结论 首次PCI术后携带CYP2C19突变基因纯合子或杂合子(CYP2C19 *2/*2、CYP2C19* 3/*3或CYP2C19* 2/*3)的患者建议使用联合抗凝治疗.