经皮冠状动脉介入术后患者CYP2C19基因多态性与氯吡格雷抵抗的相关性研究

Relationship between CYP2C19 polymorphism and clopidogrel resistance in patients with percutaneous coronary intervention

目的:探讨中国江苏地区经皮冠状动脉介入治疗(PCI)术后患者细胞色素P450 2C19(CYP2C19)基因多态性与氯吡格雷抵抗(CR)发生的关系。方法:入选191例PCI术后患者,采集患者静脉血测定20μmol/LADP诱导的最大血小板聚集率(MPA),根据MPA>50%时即为CR,将所有入选患者分为CR组(46例)和非CR组(145例)。提取基因组DNA,应用基质辅助激光解吸电离飞行时间质谱技术检测CYP2C19*2及CYP2C19*3的基因多态性。结果:CR组CYP2C19基因型分布分别为野生纯合型9例(19.6%)、突变杂合型25例(54.3%)及突变纯合型12例(26.1%),非CR组分别为73例(50.3%)、59例(40.7%)及13例(9.0%),2组间CYP2C19的3种不同基因型分布差异有统计学意义(P<0.01)。CYP2C19野生纯合型、突变杂合型和突变纯合型出现CR的概率分别为11.0%、29.8%和48.0%(P<0.01)。结论:CYP2C19基因多态性与CR的发生具有相关性,CYP2C19*2、CYP2C19*3基因突变可能使PCI术后患者发生CR的危险性增加。

Objective ： To investigate the relationship between CYP 2 C 1 9 gene polymorphism and elopidogrel resistance （CR） in percutane.ous coronary intervention （PCI） in Jiangsu district. Method： A total of 191 patients with PCI were enrolled. The maximum platelet aggregation rate （MPA） was determined when platelets were stimulated by 20 umol/L ADP. All the patients were divided into CR group （n=46） and non-CR group （n= 145） according to MPA （MPA〉50% was defined as CR）. Genomic DNA was extracted from venous blood samples based on standard protocols, and the CYP2C19 ＊ 2 and CYP2C19 ＊ 3 gene polymorphisms were genotyped by MALDI-TOF in all patients. Result：The frequencies of the three kinds of genotypes （wild-type homozygotes, heterozygous and mutation homozygous） of CYP2C19 were 19.6%, 54.3%, 26.1% in CR group and 50.3%, 40.7%, 9.0% in non-CR group, respectively. There were significant differences in the genotypes frequencies between the two groups （P〈0.01）. The incidence rates of CR in wild-type homozygotes, heterozygous and mutation homozygous were 11.0%, 29.8% and 48.0%, respectively （P〈0. 01）. Conclusion：CYP2C19 gene polymorphism is associated with the risk of CR. CYP2C19 ＊ 2 and CYP2C19 ＊ 3 gene mutation may play important roles in the occurrence of CR in patients with PCI.