冠心病患者CYP2C19基因多态性与氯吡格雷抵抗相关性研究

Correlation between CYP2C19 gene polymorphism and clopidogrel resistance in patients with coronary heart disease

目的探讨冠心病(CHD)患者CYP2C19基因多态性与氯吡格雷抵抗(CR)的相关性。方法选取2019年11—12月于北部战区总医院心血管内科确诊为CHD的206例患者为研究对象。检测CYP2C19基因型,根据基因结果将患者分为快代谢组(野生型纯合子型CYP2C19*1*1;n=79)、中代谢组(野生型与突变基因杂合子型CYP2C19*1*2、CYP2C19*1*3;n=102)和慢代谢组(突变基因纯合子与杂合子型CYP2C19*2*2、CYP2C19*2*3、CYP2C19*3*3;n=25)3组。分析各CYP2C19基因型血小板抑制率,以及CR与CYP2C19基因型之间的关系。结果快代谢组CR占36.7%(29/79),低于中代谢组的52.0%(53/102)及慢代谢组的64.0%(16/25),差异有统计学意义(χ2=4.179、5.762,P<0.05)。单因素方差分析结果显示,快代谢组、中代谢组、慢代谢组3组血小板抑制率比较,差异有统计学意义(F=3.195,P<0.05)。不同CYP2C19基因型血小板抑制率比较,差异有统计学意义(F=2.491,P<0.05)。CYP2C19基因型的曲线下面积为0.603,95%可信区间0.525~0.680,灵敏度、特异性、准确性分别为0.70、0.46、0.69。结论CHD患者CYP2C19基因型多态性与CR具有相关性,携带CYP2C19*2和/或CYP2C19*3突变基因患者易发生CR,检测CYP2C19基因型可用于指导临床抗血小板药物的应用。

Objective To investigate the correlation between CYP2 C19 gene polymorphism and clopidogrel resistance(CR)in patients with coronary heart disease(CHD).Methods A retrospective study was performed on 206 cases of patients diagnosed CHD from November to December 2019.CYP2 C19 genotype was detected,and according to the genotype,patients were divided into the fast metabolism group(wild-type homozygous CYP2 C19*1*1;n=79),medium metabolism group(wild-type and mutant heterozygous CYP2 C19*1*2,CYP2 C19*1*3;n=102)and slow metabolism group(homozygous and heterozygous mutant CYP2 C19*2*2,CYP2 C19*2*3,CYP2 C19*3*3;n=25).The platelet inhibition rate of each CYP2 C19 genotype and the relationship between CR and CYP2 C19 genotype were analyzed.Results CR in the fast metabolism group accounted for 36.7%(29/79),lower than 52.0%(53/102)in the medium metabolism group and 64.0%(16/25)in the slow metabolism group,with statistically significant differences(χ~2=4.179,5.762,P<0.05).The results of one-way ANOVA showed that the platelet inhibition rate of the fast metabolism group,the medium metabolism group and the slow metabolism group showed statistically significant differences(F=3.195,P<0.05).The difference in platelet inhibition rate between CYP2 C19 genotypes was statistically significant(F=2.491,P<0.05).The area under the curve of CYP2 C19 genotype was 0.603,the 95%CI was 0.525-0.680,and the sensitivity,specificity and accuracy were 0.70,0.46 and 0.69,respectively.Conclusion The CYP2 C19 genotype polymorphism in CHD patients is related to clopidogrel resistance.Patients with CYP2 C19*2 and/or CYP2 C19*3 mutant genes are prone to clopidogrel resistance.Detection of CYP2 C19 genotype can be used to guide clinical antiplatelet drugs application.