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中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (6): 700-704.

• 临床药理学 • 上一篇    下一篇

CYP2C19 基因多态性对癫痫患者丙戊酸血药浓度的影响

于洁1, 邵宏1, 聂小燕1, 郭金凤2, 周颖2, 崔一民2, 史录文1   

  1. 1北京大学药学院药事管理与临床药学系, 北京100083;
    2北大医院药剂科, 北京100034
  • 收稿日期:2007-02-09 修回日期:2007-04-06 发布日期:2020-11-09
  • 通讯作者: 邵宏, 男, 博士, 副教授, 硕士生导师, 研究方向:分子药物遗传学与药物基因组学。Tel:010-82801701-237 E-mail:h-shao @163. com
  • 作者简介:于洁, 女, 硕士, 研究方向:癫痫患者的药物遗传学。Tel:010-82801701-235 E-mail:yujie-916 @sina. com

Effects of CYP2C19 gene polymorphism on plasma concentration of valproic acid in patients with epilepsy

YU Jie1, SHAO Hong1, NIE Xiao-yan1, GUO Jin-feng2, ZHOU Ying2, CUI Yi-min2, SHI Lu-wen1   

  1. 1Department of Pharmacy Administration &Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China;
    2Department of Pharmacy, Peking University First Hospital, Beijing 100034, China
  • Received:2007-02-09 Revised:2007-04-06 Published:2020-11-09

摘要: 目的:研究癫痫患者CYP2C19 基因多态性与丙戊酸稳态血药浓度的关系。方法:运用PCR-RFLP方法对99 例癫痫病人的CYP2C19 *2(681G→A) 和CYP2C19 *3(636G→A) 位点进行基因型分析, 选择其中临床资料较全的88 名, 对其丙戊酸血药浓度检测结果与基因型结果进行统计学分析。结果:在99例患者中, 同时分析两个位点共5 种双位点基因型组合:681GG-636GG、 681GA-636GG、 681GG-636GA、 681AA-636GG 和681GA-636GA, 分布频率为37. 4% 、42. 4% 、6. 1% 、9. 1% 和5. 1% 。其中681AA-636GG基因型患者的丙戊酸血药浓度与体重剂量的比值明显高于野生基因型(681GG-636GG) (P<0. 05), 其他基因型与野生型相比无统计学差异。结论:本研究结果证实CYP2C19 基因多态性影响了丙戊酸血药浓度, 说明药物遗传学研究对丙戊酸临床合理用药有指导意义。

关键词: 药物遗传学, CYP2C19, 丙戊酸, 癫痫, PCRRFLP

Abstract: AIM: To determine the effect of CYP2C19 gene polymorphism on plasma concentration at steady state (Css) of valproic acid (VPA) in patients with epilepsy.METHODS: CYP2C19 variants (*2 and * 3) in 99 patients were detected using PCR-RFLP method, and 88 of them were further studied to determine the relationship between CYP2C19 polymorphism and plasma concentration of VPA.RESULTS:Studying on the *2 and *3, we found that there were five genotypes of CYP2C19 gene in these subjects, and that their frequencies were: 37. 4% for 681GG-636GG, 42. 4% for 681GA-636GG, 6. 1% for 681GG-636GA, 9. 1% for 681AA-636GG and 5. 1% for 681GA-636GA. The ratio of VPA plasma concentration to dosage was significantly higher in poor metabolizer (681AA-636GG) than in extensive metabolizer (681GG-636GG).CONCLUSION: The data suggest that CYP2C19 polymorphism significantly impacts the metabolism of VPA. The pharmacogenomics is important to rationalize the medication of VPA.

Key words: pharmacogenomics, CYP2C19, valproic acid, epilepsia, PCR-RFLP

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