CYP2C19基因多态性与氯吡格雷个体化用药的相关性研究

Correlation study of gene polymorphism of CYP2C19 and individualized medication of clopidogrel

目的:研究CYP2C19基因多态性对氯吡格雷个体化用药的影响,为氯吡格雷个体化用药提供实验室依据。方法:选取本院353例心血管内科住院患者,按CYP2C19基因型将其分为快代谢型(extensive metabolizer,EM)、中间代谢型(intermediate metabolizer,IM)、慢代谢型(poor metabolizer,PM)3组;按临床用药调整方案的不同将这353例患者分为A组(增加氯吡格雷用药的剂量)、B组(氯吡格雷与阿司匹林、西洛他唑等联合用药)、C组(停止使用氯吡格雷,换用替格瑞洛等新药),在3个用药方案不同的分组中对CYP2C19基因型检测结果进行统计分析,然后将理论上基因型结果所对应的用药方案与临床基因检测前后用药方案进行比较,若基因检测后用药方案按照理论上的用药方案进行调整,就认为两者是符合的,再计算两者的符合率,验证CYP2C19基因多态性检测对氯吡格雷个体化用药的临床指导意义。结果:353例患者CYP2C19基因多态性检测结果中EM占43.91%,IM占42.78%,PM占13.31%。IM中改变用药方案的占25.83%,其中A组占41.03%,B组占48.71%,C组占10.26%;PM中改变用药方案的占48.94%,其中A组占26.09%,B组占30.43%,C组占43.48%;IM患者以增加氯吡格雷剂量和氯吡格雷与阿司匹林、西洛他唑等联合用药这两种用药方案为主;PM患者以换用替格瑞洛等新药为主。结论:携带有CYP2C19突变型基因的患者,对氯吡格雷有不同程度的抵抗作用,临床在使用氯吡格雷前应先参考CYP2C19基因型。CYP2C19基因多态性检测对氯吡格雷个体化用药有指导作用。

Objective:To explore the impact of CYP2C19 gene polymorphisms on individualized medication of clopidogrel,and to provide some references about rational and individualized medication in clinic.Methods:353 patients with coronary disease hospitalized in the Vasculocardiology Depatment were enrolled.These patients were divided into three groups by genotypes-Group EM(extensive metabolizer),Group IM(inter mediate metabolizer)and Group PM(poor metabolizer).Meanwhile,these 353 patients were divided into three groups by clopidogrel therapy-Group A(increasing the dosage of clopidogrel),Gruop B(combining clopidogrel with other antiplatelet agents)and Group C(replacing clopidogrel with Ticagrelor Tablets).After making statistical analysis of CYP2C19 genotypes of these three groups,the therapies that were corresponded to CYP2C19 genotypes in techenique would be compared with the clinical therapies during genotypes testing.These two therapies were coincident if the therapies after genotypes testing were adjusted according to the therapies in theory.The rates of coincidence of these two therapies were to be calculated.As a result,the clinical significance that genetic polymorphisms of CYP2C19 guided rational medication of clopidogrel was validated.Results:The frequency of the Group EM in these 353 patients was 43.91%,the Group IM was 42.78%,the Group PM was 13.31%.The frequency of patients changed their therapy was 25.83%in the Group IM,while the Group A was 41.03%,the Group B was 48.71%,and the Group C was 10.26%.The frequency of patients changed their therapy was 48.94%in the Group PM,while the Group A was 26.09%,the Group B was 30.43%,and the Group C was 43.48%.In the Group IM,the most of patients gave priority to the treatment that was increasing the dosage of clopidogrel and using clopidogrel combinations.In the Group PM,most patients gave priority to the treatment that was replacing clopidogrel with mew antiplatelet drugs like Ticagrelor Tablets.Conclusions:Patients carrying CYP2C19 mutation genes have different degrees of resistance to clopidogrel.Before clopidogrel is used,we should refer to the CYP2C19 genotype.The detection of CYP2C19 gene polymorphism has a guiding role in the individualized drug use of clopidogrel.