中国人群癫痫患者CYP2C19、CYP2C9的基因型对丙戊酸清除率影响的研究

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (12): 1405-1410.

中国人群癫痫患者CYP2C19、CYP2C9的基因型对丙戊酸清除率影响的研究

白旬荣, 姜德春, 王育琴, 齐晓涟

首都医科大学宣武医院药剂科,北京 100053

收稿日期:2007-03-22 修回日期:2007-11-28 出版日期:2007-12-26 发布日期:2020-11-10
通讯作者: 王育琴,女,教授,硕士生导师,研究方向:临床药理学和临床药学。Tel:010-83198682 E-mail:yuqpwang@sina.com
作者简介:白向荣,男,临床药理学在读硕士生。Tel:010-83198352 E-mail:nunyu081@yahoo.com.cn
基金资助:
国家自然科学基金资助项团(30672504)

Effects of CYP2C19 and CYP2C9 genotype on valproate clearance in patients with epilepsy in China

BAI Xiang-rong, JIANG De-chun, WANG Yu-qin, QI Xiao-lian

Department Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 10053, China

Received:2007-03-22 Revised:2007-11-28 Online:2007-12-26 Published:2020-11-10

摘要/Abstract

摘要： 目的: 阐明中国人群癫痫患者CYP2G₁9和CYP2C9的基因多态性对丙戊酸清除率的影响。方法: 收集216例癫痫患者的一般生物学资料和临床常规监测的丙戊酸(VPA)稳态血药浓度(谷浓度)数据提取血样中白细胞的DNA并进行PCR扩增,用限制性片断长度多态性技术(RFLP)分别检测CYP2G₁9和CYP2C9的基因型依据不同的基因型,将病人分为3组:G₁、G₂和G₃。G₁组:野生型; G₂组:突变杂合型;G₃组:突变纯合型。分别求算3组患者稳态血药谷浓度与每日公斤体重药量的比值,即丙戊酸的清除率。采用多元回归分析法推算不同基因型对丙戊酸清除率的影响。结果: 216 例病人中,G₁、G₂、G₃组人数分别为86、86、44。3组患者稳态血药谷浓度分别为:(54.13±21.53)、(54.43±18.86)、(62.55±25. 62) μg/mL; 清除率分别为(11.49±4.47)、(11.13±4.95)、(9.40±4.67)mL·h^-1·kg^-1。每种基因型均和丙戊酸的清除率具有相关性。采用多元回归分析求得回归方程为:G₁组:Y= 7.395+0.299 mg·kg^-1·d^-1;G₂组:Y =4.503±0.473 mg·kg^-1·d^-1;G₃组: Y= 5.025+0.335 mg·kg^-1·d^-1。CYP2G₁9 和CYP2C9的不同基因型对丙戊酸清除率的影响具有统计学意义且G₃组患者的清除率明显低于G₁组和G₂组。结论: CYP2G₁9、CYP2C9的基因型对丙戊酸的清除率有影响,交变纯合型患者丙戊股的清除率明显低于野生型和突变杂合型的患者,应依据基因型进行个体化用药。

关键词: 基因型, 清除率, 丙戊酸, 癫痫, CYP2C9、CYP2C19

Abstract: AIM: To evaluate the effects of CYP2G₁9 and CYP2C9 gene polymorphisms on Val-proate (VPA) clearance of epileptic patients in China inorder to promote individualized medicine. METHODS: The demographic data and steady plateau concentrations of VPA frorn 216 epileptic patients to tetrospectively collect-ed.The gene polymorphisms of CYP2CI9 and CYP2C9 were examined by polymerase chain reaction-restriction fragment length polynorphism (PCR-RFLP). Accondingto the genotype of CYP2G₁9 and CYP2C9, these pa-tients were divided into three groups: G₁ (wild type),G₂(heterozygous type),G₃(homozygous type). Themean of VPA oral clearance CL/F) was calculated foreach group, and was compared among three groups. The relationship between mean of VPA oral clearance and genepoly morphism was character rizedby multiple regression analysis. RESULTS: In 216 cases of Chinese patients, the number of patients in each group was 86(G₁) 86(G₂) and 44(G₃). The mean plateau concentrations in three groups were (54.13± 21.53),(54.43±18.86), (62.55±25.62) μg/mL, and CLIF of VPA were (11.49±4.47),(11.13±4.95),(9.40±4.67) mL^-1·h^-1·kg^-1, respectively. The CLIF of VPA in G₃ group was lower than those in the other two groups. There was significant correlation between genotype and VPA oralcle arance. The regression equation were as following: G₁ group:Y=7.395+0.299 mg^-1·kg^-1·d^-1, G₂ group: y=4.503+0.473ng,G₃ group: y=5.025+0.335 mg^-1·kg^-1·d^-1. CONCLUSION: The polynorphisms of CYP2G₁9 and CYP2C9 have effect the VPA oral clearance. The CLIF of VPA in ho-mozygous typeis significantly lowered than one in het-erocygous type. It will be valuable to failitate individual-ized usage of VPA according to the genotype in elinicaltherapy.

Key words: genotype, ciearance, valproate, epilepsy, restrition fragment length polymorphism

中图分类号:

R969

白旬荣, 姜德春, 王育琴, 齐晓涟. 中国人群癫痫患者CYP2C19、CYP2C9的基因型对丙戊酸清除率影响的研究[J]. 中国临床药理学与治疗学, 2007, 12(12): 1405-1410.

BAI Xiang-rong, JIANG De-chun, WANG Yu-qin, QI Xiao-lian. Effects of CYP2C19 and CYP2C9 genotype on valproate clearance in patients with epilepsy in China[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(12): 1405-1410.

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