CYP2C19基因多态性检测指导下的伏立康唑治疗侵袭性真菌感染患者效果的评价

doi:10.3969/j.issn.1006-7795.2018.03.020

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (3): 423-427.doi: 10.3969/j.issn.1006-7795.2018.03.020

CYP2C19基因多态性检测指导下的伏立康唑治疗侵袭性真菌感染患者效果的评价

牛丙寅, 王冠, 陈世才, 翁以炳

首都医科大学附属北京潞河医院急救医学部, 北京 101100

收稿日期:2017-07-28 出版日期:2018-05-21 发布日期:2018-06-11
通讯作者: 翁以炳 E-mail:wengyibing@medmail.com.cn
基金资助:
北京市通州区科委精准医学专项（KJ2016CX037-24）。

Evaluation of voriconazole guided by CYP2C19 gene polymorphism in the treatment of patients with invasive fungal infection

Niu Bingyin, Wang Guan, Chen Shicai, Weng Yibing

Intensive Care Unit, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China

Received:2017-07-28 Online:2018-05-21 Published:2018-06-11
Supported by:
This study was supported by Precision Medicine Project of Science and Technology Commission(KJ2016CX037-24).

摘要/Abstract

摘要： 目的通过检测CYP2C19基因多态性评价对侵袭性真菌感染重症患者伏立康唑标准化治疗的效果，为临床合理用药提供参考。方法通过非随机对照研究方法，比较使用基因检测方法指导伏立康唑使用方案、以及常规伏立康唑治疗方案两种方法对侵袭性真菌感染患者的治疗效果、不良反应以及费效比。PCR-RFLP方法用于检测患者CYP2C19的基因多态性。结果共纳入80例样本，包括40例进行了基因分型检测的试验组，40例非同期诊断为侵袭性真菌感染进行常规伏立康唑治疗的对照组。基因检测者分析CYP2C19 3个位点，共有5种双位点基因型组合，包括：高代谢型（extensive metabolizer，EM）的681GG-636GG、中代谢型（intermediate metabolizer，lM）的681GA-636GG和681GG-636GA以及低代谢型（poor metabolizer，PM）的681AA-636GG和681GA-636GA，其分布频率分别为12.17%、52.16%、6.22%、17.54%和11.91%。治疗效果、费效比和不良反应方面，EM组、IM组和PM组中差异有统计学意义（P<0.05），且PM组高于IM组，IM组高于EM组（P<0.05）。与对照组的回顾性对比显示，试验组的平均住院天数及抗真菌治疗费用明显低于对照组。结论监测CYP2C19基因多态性并指导伏立康唑用药，可对剂量、疗效、不良反应和抗真菌治疗费用产生显著影响。这提示基因检测指导临床合理使用伏立康唑具有重要的社会和经济效益。

关键词: 伏立康唑, CYP2C19, 基因多态性, 侵袭性真菌感染, 重症患者

Abstract: Objective To determine effects of CYP2C19 gene polymorphism on standardized treatment of voriconazole in critically ill patients with invasive fungal infections and provide reference for clinical rational medication.Methods A non-randomized controlled study was used to compare the therapeutic efficacy, adverse reactions, and cost-effectiveness of genetically-directed voriconazole regimens and conventional voriconazole regimens in patients with invasive fungal infections. The PCR-RFLP method was used to detect the genetic polymorphism of CYP2C19 in patients.Results A total of 80 samples were included, including 40 test groups that were genotyped and 40 non-contemporaneous controls that were treated with conventional voriconazole for invasive fungal infections. The gene testers analyzed three sites of CYP2C19, a total of five two-site genotype combinations, including:681GG-636GG of an extensive metabolizer (EM), 681GA-636GG of an intermediate metabolizer (lM), and frequencies of 681GG-636GA and poor metabolites (PM) 681AA-636GG and 681GA-636GA were 12.17%, 52.16%, 6.22%, 17.54% and 11.91%, respectively. The therapeutic effect, cost-effectiveness and adverse reactions were significantly different in the EM group, IM group and PM group (P<0.05), and the PM group was significantly higher than the IM group, and the IM group was significantly higher than the EM group (P<0.05). Retrospective comparison with the control group showed that the experimental group was significantly lower than the control group in the average length of hospital stay and antifungal treatment costs.Conclusion CYP2C19 polymorphism can significantly impact the cost of standardized treatment,dosage, effects and adverse reactions of voriconazole,indicating that pharmacogenetics is important for rationalized medication of voriconazole.

Key words: voriconazolc, CYP2C19, polymorphism, invasive fungal infections, critically ill patients

中图分类号:

R459.7

牛丙寅, 王冠, 陈世才, 翁以炳. CYP2C19基因多态性检测指导下的伏立康唑治疗侵袭性真菌感染患者效果的评价[J]. 首都医科大学学报, 2018, 39(3): 423-427.

Niu Bingyin, Wang Guan, Chen Shicai, Weng Yibing. Evaluation of voriconazole guided by CYP2C19 gene polymorphism in the treatment of patients with invasive fungal infection[J]. Journal of Capital Medical University, 2018, 39(3): 423-427.

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CYP2C19基因多态性检测指导下的伏立康唑治疗侵袭性真菌感染患者效果的评价

Evaluation of voriconazole guided by CYP2C19 gene polymorphism in the treatment of patients with invasive fungal infection

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