CYP2C19、PON1基因多态性与脑梗死患者氯吡格雷治疗预后的相关性研究

摘要

目的:探讨大动脉粥样硬化型脑卒中(LAA)患者服用氯吡格雷短期预后与CYP2C19、PON1基因多态性的关系.方法:对最终入组的96例首发LAA患者给予阿司匹林联合氯吡格雷治疗30 d,后氯吡格雷单药长期治疗,治疗前及3个月后对患者进行改良RANKIN量表(mRS)评分,mRS≤2表示预后好,mRS>2表示预后差;使用非扩增荧光染色原位杂交技术进行基因分型.通过比较各种基因型与mRS评分的相关性,判断患者预后与上述两种基因的基因多态性之间的关系,mRS≤2表示预后好,mRS>2表示预后差.结果:治疗前,CYP2C19三种不同基因型与患者mRS评分无统计学差异,3个月后,CYP2C19三种基因型与mRS评分有统计学差异(P＜0.05),携带有CYP2C19 EM型等位基因的患者预后较好(P＜0.05),即未携带CYP2C19无功能等位基因的患者预后较携带者好.治疗前,PON1 (576G>A)三种基因型与患者mRS评分无统计学差异,3个月后预后改善在三种基因型之间亦无统计学差异(P>0.05).结论:大动脉粥样硬化性卒中患者服用氯吡格雷后短期预后与 CYP2C19基因多态性有关.%Objective:To investigate the relationship between CYP2C19 and PON1 gene polymorphisms and the prognosis in patients with large artery atherosclerotic stroke following medication of clopidogrel.Methods: Ninety-six patients with first large artery atherosclerotic stroke attack were included and given clopidogrel plus aspirin medication for 30 days,followed by simple chronic clopidogrel regimen.Modified RANKIN scale(mRS)was used before and 3 months after medication to assess the therapeutic effects.Patients with mRS scoring ≤ 2 were considered as ′good prognosis′,and those with mRS scoring>2 were considered as ′poor prognosis′.The genotypes of CYP2C19 and PON1 (576G>A) were detected with non-amplified fluorescent dyes in situ hybridization technique,and compared with the mRS scoring for estimating the relationship between the CYP2C19 and PON1 (576G>A) polymorphisms and prognosis following medication.Results: The difference was not significant between mRS scores and different three genotypes of CYP2C19 in patients before therapy,yet the difference was significant 3 months after medication(P<0.05),and patients with CYP2C19 EM alleles had better prognosis than those with CYP2C19 with loss-of-functional alleles(P<0.05).The three genotypes for PON1 (576G>A) remained no statistical difference with mRS scores before therapy 3 months after medication(P>0.05).Conclusion: The prognosis appears to be associated with CYP2C19 gene polymorphism in patients with large artery atherosclerotic stroke following short use of clopidogrel.