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

Abstract

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

CLC Number:

R969

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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