Impact of MDR1 and UGT Gene Polymorphisms on Sodium Valproate Plasma Concentration in Patients with Epilepsy

This study aimed to identify the effects of multidrug resistance gene 1 (MDR1) and UGT gene polymorphisms on the plasma concentration of VPA in subjects with epilepsy and provide a reference for individualized medicine of patients with epilepsy.

One hundred subjects with epilepsy who were treated with sustained release VPA monotherapy were enrolled. Sanger sequencing was used to detect the genotypes of MDR1_G1199A, MDR1_G2677T/A, UGT1A6_A 552C, T19G and UGT2B7_C161T. By adjusting the plasma concentrations of VPA with body weight and a total daily dose of VPA, the concentration-to-dose ratio of VPA (CDRV) was obtained. Data were analyzed using SPSS17.0.

No mutation of MDR1_G1199A gene was detected. MDR1_G2677T/A site T allele frequency is 43.5%, A is 14%. The genetic frequencies of UGT1A6_A552C, T19G, and UGT2B7_C161T were 29.5%, 25.5%, and 36%, respectively. Significant differences in CDRV were observed between carriers of TT, TG, and GG genotypes in the UGT1A6_T19G polymorphism (p = 0.021, p < 0.05). The CDRV was significantly lower in patients carry UGT1A6_T19G GG genotype compared to TG ((3.40 ± 1.61) μg.kg/mL.mg) and TT ((4.33 ± 1.97) μg.kg/mL.mg) genotype. While the MDR1_G2677T/A, UGT1A6_A552C and UGT2B7_C161T gene polymorphisms had no effect on the plasma concentration of VPA (p > 0.05).

The genetic polymorphisms of UGT1A6_T19G significantly affect the plasma concentration of VPA in patients with epilepsy and the mutation of this locus can decrease the blood concentration of VPA. The MDR1_G2677T/A, UGT1A6_A552C and UGT2B7_C161T gene polymorphisms did not affect the plasma VPA concentration in Han patients with epilepsy.