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  • Title: Impact of MDR1 and UGT Gene Polymorphisms on Sodium Valproate Plasma Concentration in Patients with Epilepsy.
    Author: Song C, Li X, Zhang H, Bao J, Lu W, Peng Q, Zhang Y.
    Journal: Clin Lab; 2022 Oct 01; 68(10):. PubMed ID: 36250837.
    Abstract:
    BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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