CYP2C19基因多态性对老年急性脑梗死患者应用氯吡格雷临床预后的影响

doi:10.12092/j.issn.1009-2501.2020.09.008

中国临床药理学与治疗学 ›› 2020, Vol. 25 ›› Issue (9): 1014-1020.doi: 10.12092/j.issn.1009-2501.2020.09.008

CYP2C19基因多态性对老年急性脑梗死患者应用氯吡格雷临床预后的影响

许宏磊¹，徐炳欣¹，俎青²，赵艳¹，高朋飞²，于洋²

¹许昌市中心医院药学部，许昌市心血管药物临床研究重点实验室，许昌 461000，河南；²许昌市中心医院神经内科，许昌 461000，河南

收稿日期:2020-04-03 修回日期:2020-07-24 出版日期:2020-09-26 发布日期:2020-09-30
通讯作者: 徐炳欣，男，硕士，副主任药师，研究方向：药物基因组学与个体化给药。 Tel: 0374-3353597 E-mail: xin4891@126.com
作者简介:许宏磊，男，硕士，主管药师，研究方向：医院药学与个体化给药。 Tel: 0374-3353597 E-mail: xhl3597@126.com
基金资助:
2018年中央引导地方科技发展专项资金支持项目（豫财科［2018］106号）；许昌市重大科技专项（20180113031）

Effects of CYP2C19 gene polymorphism on the clinical prognosis of clopidogrel in elderly patients with acute cerebral infarction

XU Honglei ¹, XU Bingxin ¹, ZU Qing ², ZHAO Yan¹, GAO Pengfei ², YU Yang²

¹ Department of Pharmacy, Xuchang Key Laboratory of Cardiovascular Drugs Clinical Research, Xuchang Central Hospital, Xuchang 461000, Henan, China; ² Department of Neurology, Xuchang Central Hospital, Xuchang 461000, Henan, China

Received:2020-04-03 Revised:2020-07-24 Online:2020-09-26 Published:2020-09-30

摘要/Abstract

摘要： 目的：探讨CYP2C19基因多态性对老年急性脑梗死患者应用氯吡格雷临床预后的影响。方法：前瞻性纳入接受阿司匹林联合氯吡格雷治疗的226例老年急性脑梗死患者，采用DNA微阵列芯片法检测CYP2C19基因型并据此将患者分为快代谢组、中等代谢组和慢代谢组，记录患者治疗前后美国国立卫生研究院卒中量表（National Institute of Health Stroke Scale, NIHSS）评分，重复测量资料方差分析研究三组NIHSS评分变化，以治疗前后NIHSS评分的下降幅度为标准评价患者预后，比较三组预后良好率的差异，二元Logistic回归分析探讨急性脑梗死预后的影响因素，观察三组药品不良反应（adverse drug reaction, ADR）发生情况。结果：快代谢组、中等代谢组、慢代谢组分别有81例（35.8%）、108例（47.8%）和37例（16.4%）患者，预后良好率分别为86.4%，73.1%和64.9%，三组预后良好率差异有统计学意义（P<0.05），且快代谢组显著高于慢代谢组（P<0.05）。重复测量资料方差分析显示，三组NIHSS评分随时间的变化趋势不同，且治疗后快代谢组NIHSS评分显著低于中等代谢组和慢代谢组（P<0.05）；二元Logistic回归分析显示，快代谢组患者应用氯吡格雷临床预后良好的概率是慢代谢组患者的3.447倍（OR=3.447, 95%CI: 1.364-8.712, P=0.009），有糖尿病患者应用氯吡格雷临床预后良好的概率是无糖尿病患者的62.7%（OR=0.627, 95%CI: 0.268-1.331, P=0.001）。三组ADR总发生率相近（P>0.05）。结论：CYP2C19基因多态性对老年急性脑梗死患者应用氯吡格雷临床预后有影响，且快代谢型患者治疗效果优于慢代谢型。

关键词: CYP2C19, 基因多态性, 急性期脑梗死, 氯吡格雷, 预后

Abstract: AIM: To investigate the effect of CYP2C19 gene polymorphism on the clinical prognosis of elderly patients treated with clopidogrel who suffered acute cerebral infarction. METHODS: A total of 226 elderly patients with acute cerebral infarction who received aspirin and clopidogrel were prospectively enrolled in this study. The CYP2C19 genotype was detected by DNA microarray chip method. Based on CYP2C19 genotypes, the patients were divided into fast metabolism group, medium metabolism group and slow metabolism group. The National Institutes of Health Stroke Scale (NIHSS) scores before and after treatment were recorded. The changes of NIHSS scores before and after treatment were studied by repeated measurement ANOVA (analysis of variance), the decrease of NIHSS scores before and after treatment was used as the standard to evaluate the prognosis of patients, and the difference of favorable prognosis rate was compared among the three groups. Binary logistic regression analysis was used to explore the prognosis influencing factors of acute cerebral infarction, and adverse drug reactions (ADR) were observed in the three groups. RESULTS: There were 81 patients (35.8%), 108 patients (47.8%) and 37 patients (16.4%) in fast metabolism group, medium metabolism group and slow metabolism group, respectively, with a favorable prognosis rate of 86.4%, 73.1% and 64.9% respectively. There was significant difference in the favorable prognosis rate among the three groups, and fast metabolism group was significantly higher than slow metabolism group (P<0.05). Repeated measurement ANOVA showed that the NIHSS scores of three groups varied with time, and the NIHSS scores of fast metabolism group after treatment were lower than those of medium metabolism group and slow metabolism group, the difference was statistically significant (P<0.05). Binary logistic regression analysis showed that patients in fast metabolism group had a favorable clinical prognosis 3.447 times as much as those in slow metabolism group (OR=3.447, 95% CI: 1.364-8.712, P=0.009). Patients with diabetes had a favorable clinical prognosis 62.7% as those without diabetes (OR=0.627, 95% CI: 0.268-1.331, P=0.001). There was no statistical difference in the total incidence of ADR among the three groups (P>0.05). CONCLUSION: CYP2C19 gene polymorphism has an effect on the clinical prognosis of elderly patients treated with clopidogrel who suffered acute cerebral infarction, and the therapeutic effect on rapid metabolizer is better than that of slow metabolizer.

Key words: CYP2C19, gene polymorphism, acute cerebral infarction, clopidogrel, prognosis

中图分类号:

R969

许宏磊, 徐炳欣, 俎青, 赵艳, 高朋飞, 于洋. CYP2C19基因多态性对老年急性脑梗死患者应用氯吡格雷临床预后的影响[J]. 中国临床药理学与治疗学, 2020, 25(9): 1014-1020.

XU Honglei, XU Bingxin, ZU Qing, ZHAO Yan, GAO Pengfei, YU Yang. Effects of CYP2C19 gene polymorphism on the clinical prognosis of clopidogrel in elderly patients with acute cerebral infarction[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(9): 1014-1020.

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CYP2C19基因多态性对老年急性脑梗死患者应用氯吡格雷临床预后的影响

Effects of CYP2C19 gene polymorphism on the clinical prognosis of clopidogrel in elderly patients with acute cerebral infarction

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