CYP2C19基因多态性与脑梗死患者氯吡格雷临床疗效的相关性研究

Correlation between CYP2C19 gene polymorphisms and efficacy of clopidogrel in patients with cerebral infarction

关键词:  脑梗死  氯吡格雷  CYP2C19  基因多态性

Key words:  cerebral infarction  clopidogrel  CYP2C19  gene polymorphisms

摘要:

目的 探究CYP2C19基因多态性与氯吡格雷治疗脑梗死患者疗效的相关性。方法 选取我院2012年1月至2015年1月的脑梗死患者200例。根据基因型分为高、中间、弱代谢型三组。统计口服氯吡格雷前、第1天、第6天、第8周患者的血小板聚集抑制率、美国国立卫生研究院脑卒中量表(National Institute of Health stroke scale, NIHSS)评分、日常生活能力评分(Activities of Daily Living, ADL)和1年内心脑血管不良事件的发生率。结果治疗后第1天和第6天,三组血小板聚集抑制率差异均有统计学意义(P＜0.05),由高到低依次为强、中间、弱代谢型组,两两比较差异明显,第6天和第8周差异无统计学意义。治疗后1、3和6个月,三组NIHSS、ADL评分差异均有统计学意义(P＜0.05),治疗效果由高到低依次为高、中间、弱代谢型组,两两比较差异明显。1年内强代谢型组心脑血管不良事件总的发生率明显低于中间和弱代谢型组,差异具有统计学意义(P＜0.05)。结论 CYP2C19基因多态性与脑梗死患者氯吡格雷治疗效果与预后有关,其机制可能与代谢酶活性有关。

Abstract:

Objective To investigate the correlation between CYP2C19 gene polymorphisms and the efficacy of clopidogrel in patients with cerebral infarction. Methods Two hundred patients with cerebral infarction treated in our hospital from January 2012 to January 2015 were included in the study. The DNA was extracted from blood samples and the CYP2C19 gene polymorphisms were detected by PCR-RFLP. According to the genotypes of CYP2C19 gene, patients were divided into extensive metabolic group, intermediate metabolic group and poor metabolic group. The impedance platelet aggregometry was measured, the National Institute of the Health stroke scale (NIHSS), activities of daily living (ADL) were assessed before and 1^st, 6^th day and 8^th week after clopidogrel administration. The incidence of cerebro-cardiovascular events in one year were documented. ResultsThe impedance platelet aggregometry in extensive metabolic group was the highest 1^st day and 6^th day after treatment, followed by the intermediate, and that was the lowest in the poor group (P<0.05), there was no statistical significance between that in the 6^th day and 8 weeks. There were significant differences in NIHSS and ADL scores at the first, third and the sixth month after treatment among three groups (P<0.05), and the improvement in extensive group was the best, followed by intermediate and the poor groups. The incidence of cerebro-cardiovascular events of extensive metabolic group in one year was significantly lower than that of other two groups (P<0.05). Conclusion CYP2C19 gene polymorphisms are associated with the efficacy of clopidogrel in patients with cerebral infarction, which may be related to the activation of metabolic enzymes.