CYP2C19基因多态性对氯吡格雷治疗缺血性脑卒中患者复发率的影响

Effect of CYP2C19 Gene Polymorphism on the Recurrence Rate of Ischemic Stroke Patients Treated with Clopidogrel

目的调查CYP2C19基因多态性对氯吡格雷治疗缺血性脑卒中患者复发率的影响。方法入组289例缺血性脑卒中患者,采用CYP2C19基因检测试剂盒检测患者的CYP2C19基因型。通过随访,分析CYP2C19基因多态性对氯吡格雷治疗缺血性脑卒中患者复发率的影响。结果通过对患者1~12个月的随访,289例患者中有41例(14.9%)患者发生脑卒中复发。中间代谢型和慢代谢型的复发风险均高于快代谢型,具有统计学意义(OR=2.9, 95%CI:1.3~6.3,P=0.0068;OR=3.0,95%CI:1.1~8.2,P=0.027)。携带*2(681A)A等位基因的患者,卒中复发风险高于携带*1(681G)G等位基因的患者(OR=3.3,95%CI:1.3~8.8,P=0.0065);基因型CYP2C19*1/*2的卒中复发风险高于基因型CYP2C19*1/*1(OR=2.0,95%CI:0.9~4.1,P=0.071);基因型CYP2C19*2/*2的卒中复发风险高于基因型CYP2C19*1/*1 (OR=3.3,95%CI:1.3~8.8,P=0.012);携带*3(636A)A等位基因的卒中复发风险与基因型CYP2C19*1/*1相比没有统计学差异。对缺血性脑卒中患者复发组和非复发组危险因素进行单因素回归分析显示,具有统计学差异的危险因素包括携带CYP2C19*2、*3等位基因(P=0.004)、高血压(P=0.040)、高同型半胱氨酸血症(P=0.007)和合并药物ACEI/ARB(P=0.006)。以单因素分析P<0.05的因素为自变量进行多因素回归分析,结果提示,携带CYP2C19*2、*3等位基因和高同型半胱氨酸血症是缺血性脑卒中复发的独立危险因素。结论中间代谢和慢代谢基因型缺血性脑卒中患者卒中复发率高于快代谢基因型患者,且携带CYP2C19*2、*3等位基因和高同型半胱氨酸血症是缺血性脑卒中复发的独立危险因素。

OBJECTIVE To investigate the effect of CYP2C19 polymorphism on the recurrence rate of ischemic stroke patients treated with Clopidogrel.METHODS A total of 289 patients with ischemic stroke were recruited.CYP2C19 gene testing kit was used to detect the genotype of CYP2C19.The influence of CYP2C19 gene polymorphism on the recurrence rate of patients with ischemic stroke treated with Clopidogrel was analyzed through follow-up.RESULTS After 1~12 months of follow-up,41(14.9%)of the 289 patients experienced recurrent stroke.The risk of recurrence for intermediate and slow metabolisms was higher than that for fast metabolisms,with statistical significance(OR=2.9;95%CI,1.3 to 6.3;P=0.006 8;OR=3.0;95%CI,1.1 to 8.2;P=0.027).The risk of stroke recurrence with*2(681A)A allele was higher than with*1(681G)G allele(OR=3.3;95%CI,1.3 to 8.8;P=0.006 5);The risk of stroke recurrence of genotype CYP2C19*1/*2 was higher than that of genotype CYP2C19*1/*1(OR=2.0;95%CI,0.9 to 4.1;P=0.071).The risk of stroke recurrence of genotype CYP2C19*2/*2 was higher than that of genotype CYP2C19*1/*1(OR=3.3;95%CI,1.3 to 8.8;P=0.012);The risk of stroke recurrence with the*3(636A)A allele was not statistically different from the genotype CYP2C19*1/*1.Univariate regression analysis of risk factors for recurrent and non-recurrent ischemic stroke patients showed that risk factors with statistical differences included CYP2C19*2,*3 allele(P=0.004),Hypertension(P=0.040),Hyperhomocysteinemia(Hcy)(P=0.007),and combined drugs(ACEI/ARB)(P=0.00 6).Multivariate regression analysis was performed using factors with a single factor analysis P<0.05 as the independent variable.The results suggested that CYP2C19*2,*3 allele and high Hcy were independent risk factors of ischemic stroke recurrence.CONCLUSION The recurrence rate of ischemic stroke in patients with intermediate metabolism and slow metabolism genotypes was higher than that in patients with fast metabolism genotypes,and CYP2C19*2,*3 allele and high Hcy were independent risk factors of ischemic stroke recurrence.