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ABCB1和CYP2C19基因多态性与动脉粥样硬化性脑梗死患者氯吡格雷疗效的相关性

Correlation between ABCB1 and CYP2C19 genotype and efficacy of clopidogrel in patients with atherosclerotic cerebral infarction

  • 摘要:
    目的 探讨在急性动脉粥样硬化性脑梗死患者中,不同ABCB1和CYP2C19基因型对氯吡格雷抗血小板疗效的影响。
    方法 纳入115例发病7 d内住院的急性动脉粥样硬化性脑梗死患者,根据CYP2C19基因型分为3组:快代谢型、中代谢型、慢代谢型;根据ABCB1基因型分为野生型和突变型。再根据ABCB1和CYP2C19两种基因突变的数量,将入组患者分为A组(两个基因均无突变)、B组(其中一个基因发生突变)和C组(两个基因均发生突变)。所有患者均予以卒中单元常规治疗,利用血栓弹力图仪(thromb elasto gram,TEG)检测患者服用氯吡格雷7 d后的血小板功能及血小板药物抑制率,并在患者入院时及服用氯吡格雷治疗7 d后进行神经功能评估,包括美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)及改良Rankin量表(modified rankin scale,mRS)。
    结果 CYP2C19基因快代谢型、中代谢型、慢代谢型分别有46例、48例(其中*1/*2 40例,*1/*3 8例)、21例(其中*2/*2 18例,*2/*3 3例);ABCB1野生型49例,突变型66例;A、B、C组患者分别有23例、50例、42例。不同ABCB1、CYP2C19基因型及含不同基因突变数量患者中,血小板药物抑制率、血小板功能及急性期神经功能变化情况差异均无统计学意义。
    结论 在本研究所纳入的急性动脉粥样硬化性脑梗死人群中,未发现ABCB1、CYP2C19基因多态性对氯吡格雷疗效的影响。

     

    Abstract:
    Objective To explore the relationship between ABCB1 and CYP2C19 genotype and efficacy of clopidogrel in patients with acute atherosclerotic cerebral infarction.
    Methods Totally, 115 inpatients within 7 days after the onset of acute atherosclerotic cerebral infarction were assigned to three groups according to CYP2C19 genotype:extensive metabolizers, intermediate metabolizers, and poor metabolizers. Then, according to ABCB1 genotype, patients were divided into wild type and mutant type. Moreover, according to the number of gene mutations, patients were grouped into A (absence of variant CYP2C19 and ABCB1), B (either variant CYP2C19 or ABCB1), and C (both variant CYP2C19 and ABCB1). All the patients were treated with conventional treatments in the stroke unit, and thrombelastogram (TEG) was used to test platelet function and platelet inhibition ratio after patients taking clopidogrel for seven days. On admission and after taking clopidogrel for seven days, all the patients were evaluated by neurologic function scales including the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS).
    Results The patients of extensive metabolizers, intermediate metabolizers, and poor metabolizers were 46, 48 (40 *1/*2, 8 *1/*3), and 21 (18 *2/*2, 3 *2/*3), respectively. The patients of wild type and mutant type were 49 and 66. The number of patients of Group A, B, and C was 23, 50, and 42, respectively. Among different genotype of CYP2C19, ABCB1, and number of gene mutations, there were no significant differences in the platelet inhibition ratio, platelet function and neurologic function variety during the acute phase of stroke.
    Conclusions In patients with acute atherosclerotic cerebral infarction in our study, the effect of the gene polymorphism of CYP2C19 and ABCB1 on clopidogrel has not been observed.

     

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