CYP2C19*2、CYP2C19*3基因分型与急性缺血性脑卒中再发脑卒中的关系

目的探讨细胞色素P450药物代谢酶(CYP)2C19基因分型与氯吡格雷治疗的急性缺血性脑卒中患者再发脑卒中的关系。方法选取2018年5月—2018年12月常州市第一人民医院收治接受氯吡格雷治疗的159例急性缺血性脑卒中患者,检测患者入院后空腹外周血中CYP2C19*2,CYP2C19*3基因分型。对患者进行随访,随访截至2020年2月,观察再发脑卒中的情况,并分析CYP2C19*2,CYP2C19*3基因分型与再发脑卒中关系。结果随访时间14~22个月,平均随访时间为(18.2±1.5)个月,共7例患者失访,共20例(13.2%)患者复发缺血性脑卒中。再发脑卒中患者中CYP2C19*2 GG型及CYP2C19*3 GG型均低于无复发患者(P<0.05),CYP2C19*2 GA型,CYP2C19*2 AA型CYP2C19*3 GA型,CYP2C19*3AA型均高于无复发患者(P<0.05)。Kaplan-Meier法并Log-rank检验结果显示,CYP2C19*2 GG型无复发时间长于AA型,差异有统计学意义(Log-rank=6.759,P=0.034)。CYP2C19*3GG型无复发时间长于AA型,差异有统计学意义(Log-rank x2=8.660,P=0.013)。多因素Cox分析结果显示,糖尿病、氯吡格雷抵抗,CYP2C19*2及CYP2C19*3基因型是再发脑卒中影响因素(P<0.05)。结论在接受氯吡格雷治疗急性缺血性脑卒中患者中,CYP2C19*2及CYP2C19*3突变型再发脑卒中的风险明显增高。

Relationship between CYP2C19*2,CYP2C19*3 genotyping and recur-rent stroke in acute ischemic stroke

Objective To investigate the relationship between cytochrome P450 drug metabolizing enzyme(CYP)2C19genotyping and recurrent stroke in treatment of clopidogrel in patients with acute ischemic stroke(AIS).Methods 159AlS patients,aged>18,were hospitalized and treated with clopidogrel.Sample of peripheral fasting venous blood werecollected at admission and underwent PCR by base quenching probe technique to test the genotypes of CYP2C19*2 and CYP2.The patients were lowed up for(18.2±1.5)months(14-22 months)to observe the recurrent stroke and ana-lyze the relationship between CYP2C19*2 and CYP2C19*3 genotyping and recurrent stroke.Results 7 patients werelost to follow-up and 20(13.2%)had recurrent ischemic stroke.CYP2C19*2CG and CYP2C19*3 CG were lower inthe patients with recurrent stroke than in patients without recurrence(P<0.05).The rates of CYP2C19*2 GA,CYP2C19*2AA,CYP2C19*3 GA,and CYP2C19*3 AA types were all significantly higher in the patients with recur-rent stroke than in those without recurrence(all P<0.05).Kaplan-Meier method and Log-rank test results showed thatCYP2C19*2GG type has no recurrence time longer than AA type,the difference is statistically significant(Log-rank X=6.759,P=0.034).CYP2C19*3 GG type has no recurrence time longer than A A type,the difference is statistically sig-nificant(Log-rank x=8.660,P=0.013).Multivariate Cox analysis showed that diabetes,clopidogrel resistance.CYP2C19*2 genotype and CYP2C19*3 genotype were influencing factors for recurrent stroke(all P<0.05).Conclusionln the AlS patients receiving clopidogrel the risk of recurrent stroke in CYP2C19*2 and CYP2C19*3 mutants is signifi-cantly increased.