基于武汉地区PCI术后患者CYP2C19基因多态性指导氯吡格雷个体化用药的研究

目的研究CYP2C19基因多态性,分析经皮冠状动脉介入治疗(PCI)术后氯吡格雷中、慢代谢患者个体化用药的疗效差异,为PCI术后患者个体化用药提供参考依据。方法使用荧光定量PCR法测定该院328例PCI术后患者CYP2C19基因型,分析年龄、性别与CYP2C19基因多态性的关系及不同地区汉族冠心病患者代谢表型差异,比较中、慢代谢型患者维持原方案(服用氯吡格雷)和更换抗血小板药物治疗之间的疗效差异。结果本研究共检测出7种基因型,分别为CYP2C19*1*17、*1*1、*1*2、*1*3、*2*17、*2*2、*2*3;4种代谢表型,分别为超快代谢型(1.22%)、快代谢型(42.38%)、中代谢型(40.85%)、慢代谢型(15.55%);代谢表型与太原、连云港地区汉族冠心病患者比较差异有统计学意义(P<0.05),与其他地区汉族冠心病患者比较差异无统计学意义(P>0.05);不同性别患者CYP2C19基因分型、代谢表型差异无统计学意义(P=0.646、0.246);不同年龄段患者CYP2C19基因分型、代谢表型差异无统计学意义(P=0.823、0.574);中、慢代谢型患者维持原方案与更换抗血小板药物治疗比较,疗效差异无统计学意义(P=0.538)。结论本研究中的武汉地区汉族PCI术后患者以中、快代谢型为主,等位基因频率符合亚洲人群分布,对于中、慢代谢型患者,更换抗血小板药物未降低心血管不良事件发生率。

Individualized medication of Clopidogrel based on the CYP2C19 gene polymorphism in patients after PCI in Wuhan

Objective To provide a reference for the individualized medication of patients after PCI by studying the CYP2C19 gene polymorphism and analyzing the differences in efficacy of individual medication for patients with moderate or slow metabolism of Clopidogrel.Methods Real-time PCR were used to monitor the genotype of CYP2C19 for 328 patients and the correlation between sex,age and genetic polymorphism of CYP2C19 were analyzed.The metabolic phenotype of Han nationality patients with coronary heart disease(CHD)from different regions were compared.The efficacy was compared between the patients with moderate or slow metabolism who maintained the original regimen of clopidogrel and those who changed the antiplatelet drugs.Results A total of 7 genotypes were detected,which were CYP2C19*1*17,*1*1,*1*2,*1*3,*1*3,*2*17,*2*2,*2*3.The four metabolic phenotypes were ultrarapid metabolizer(1.22%),extensive metabolizer(42.38%),intermediate metabolizer(40.85%)and poor metabolizer(15.55%).The metabolic phenotype of Han patients with CHD in Wuhan was significantly different from that in taiyuan and lianyungang(P<0.05),but not significantly different from that in other regions(P>0.05).There was no significant difference between male and female patients in CYP2C19 genotype and metabolic phenotype(P=0.646,0.246).There was no significant difference among patients of different age in CYP2C19 genotype and metabolic phenotype(P=0.823,0.574).Comparison between patients who maintained the original regimen and replaced antiplatelet drugs,the curative effect were not significantly different(P=0.538).Conclusion The Han patients after PCI in Wuhan in this study are mainly extensive and intermediate metabolizer and the allele frequency is in line with the Asian population distribution.The replacement of antiplatelet agents do not reduce the incidence of adverse cardiovascular events in patients who are intermediate and poor metabolizer.