多药耐药基因单倍体对中国癫痫患者丙戊酸钠血药浓度的影响

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (11): 1267-1272.

多药耐药基因单倍体对中国癫痫患者丙戊酸钠血药浓度的影响

丁媛媛, 杨凡, 刘静, 许茜, 张梅, 许景峰

北京军区总医院药理科,北京 100700

收稿日期:2010-10-10 修回日期:2010-11-09 出版日期:2010-11-26 发布日期:2020-09-16
作者简介:丁媛媛,女,博士,主管药师,研究方向:药物基因组学。Tel: 15811084169 E-mail: dyymiss@yahoo.com.cn

Effects of the multidrug resistance 1 gene haplotype on resistance of valproic acid in Chinese Han Epilepsy patients

DING Yuan-yuan, YANG Fan, LIU Jing, XU Qian, ZHANG Mei, XU Jing-feng

Department of Pharmacology General Hospital of Beijing Military Command, Beijing 100700, China

Received:2010-10-10 Revised:2010-11-09 Online:2010-11-26 Published:2020-09-16

摘要/Abstract

摘要： 目的: 探讨多药耐药基因(MDR1)C1236T、C3435T、G26677T/A 3个SNP位点单倍型对中国汉族癫痫患者丙戊酸钠血药浓度的影响。方法: 实验选择单药服用丙戊酸钠的汉族癫痫患者143例,根据临床资料分为耐药组(n=68)和控制组(n=75),应用Pyrosequencing法测定MDR1基因C1236T、C3435T、G26677T/A多态性,同时应用荧光偏振免疫法(FPIA)测定耐药组和控制组患者丙戊酸钠的血药浓度。结果: 耐药组C3435T位点CC型发生率(66.18％)高于控制组(26.03％)(P<0.01),而CT型发生率(19.12％)则低于控制组(60.27％)(P<0.05),耐药组C1236T CT型(23.53％)低于控制组(45.33%)(P<0.05);单倍体分析结果表明,丙戊酸钠耐药组单倍型CGC(18.38%)高于控制组(9.33%)(P<0.05);单倍型TTT(10.29%)低于控制组(17.33%)(P<0.05);血药浓度检测结果表明:CGC型的血药浓度高于控制组,两组资料间血药浓度均值的差别有统计学意义(P<0.05)。结论: MDR1基因CGC单倍型影响癫痫患者丙戊酸钠血药浓度,可能是引起丙戊酸钠耐药的影响因素。

关键词: 多药耐药基因, 丙戊酸钠, 焦磷酸测序, 单倍体

Abstract: AIM: To investigate the association between valproic acid (VAP) plasma concentration and the multidrug resistance 1(MDR1)gene linkage disequilibrium among C1236T-G2677T-C3435T in Chinese Epilepsy Patients. METHODS: The study consisted of 143 epileptic patients receiving sodium valproate. The patients were divided into two groups according to the date of clinic. One was drug fast group (n=68)and the other was control group (n=75). The C1236T, C3435T and G2677T/A SNPs of MDR1 gene were determined by Pyrosequencing and sequencing analysis. Fluorescence polarization immunoassay (FPIA) was used to measure the serum concentration of sodium valproate. RESULTS: Incidence rate of CC for C3435T in drug fast group(66.18％)was higher than that in control group(26.03％)(P<0.001);Incidence rate of CT for C3435T in drug fast group(19.12％)was higher than that in control group(60.27％)(P<0.05);Incidence rate of CT for C1236T in drug fast group(23.53％)was lower than that in control group(45.33％)(P<0.05); Incidence rate of CGC in drug fast group(18.38％)was higher than that in control group(9.33％)(P<0.05);Haplotypes analysis demonstrated that the incidence rate of TTT in drug fast group(10.29％)was lower than that in control group(17.33％)(P<0.05);The mean value of the serum concentration of sodium valproate in CGC drug fast group was higher than that in CGC control group with a statistical significance (P<0.05). CONCLUSION: The haplotype of CGC of MDR1 affect the serum concentration of sodium valproate,it offers a potential mechanistic basis to explain intersubject difference in drug fast of sodium valproate.

Key words: Multidrug resistance 1, Valproate sodium, Pyrosequencing, Haplotype

中图分类号:

R969

丁媛媛, 杨凡, 刘静, 许茜, 张梅, 许景峰. 多药耐药基因单倍体对中国癫痫患者丙戊酸钠血药浓度的影响[J]. 中国临床药理学与治疗学, 2010, 15(11): 1267-1272.

DING Yuan-yuan, YANG Fan, LIU Jing, XU Qian, ZHANG Mei, XU Jing-feng. Effects of the multidrug resistance 1 gene haplotype on resistance of valproic acid in Chinese Han Epilepsy patients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(11): 1267-1272.

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