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Impact of ABCB1 Polymorphism on Levetiracetam Serum Concentrations in Epileptic Uygur Children in China.


ABSTRACT: BACKGROUND:Interindividual variations in the efficacy of antiseizure medications make epilepsy treatment challenging. This is due to genetic factors such as gene polymorphisms in Adenosine-triphosphate (ATP)-binding cassette sub-family B member 1 (ABCB1). In this article, the impact of polymorphisms in the P-glycoprotein-encoding gene, ABCB1 (C1236T, G2677T/A, and C3435T), on levetiracetam disposition was evaluated in Uygur Chinese children with epilepsy. METHODS:MDR1 C3435T polymorphism was analyzed by polymerase chain reaction-fluorescence staining in situ hybridization. The ? test and Fisher exact test were used to analyze the allelic and genotypic distribution of ABCB1, C1236T, G2677T, and C3435T between the drug-resistant and drug-responsive groups. Differences in steady-state and dose-corrected levetiracetam serum concentrations between the different genotypes were analyzed using 1-way analysis of variance and Mann-Whitney test. RESULTS:Total 245 Uygur children with epilepsy were analyzed [drug-resistant, n = 117 (males:females = 53:64) and drug-responsive, n = 128 (males:females = 76:52)]. The frequency of ABCB1 C1236T, G2677T/A, and ABCB1 C3435T genotypes, alleles, haplotypes, or diplotypes did not differ significantly between the 2 groups (P > 0.05). Significantly higher levetiracetam concentrations and serum concentration/body mass dose were seen in ABCB1 2677-GT, TT, GA, and AT genotypes and 3435-TT carriers compared with GG and CC carriers (P = 0.021 and P = 0.002 versus P = 0.001 and P = 0.000, respectively). CONCLUSIONS:ABCB1 G2677T/A and C3435T may affect levetiracetam disposition and therapeutic efficacy in Uygur children with epilepsy. Genetic analysis could be a valuable tool for predicting the response to antiseizure medications before the start of treatment and could contribute to personalized medicine for Uygur children with epilepsy.

SUBMITTER: Zhao T 

PROVIDER: S-EPMC7664979 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Impact of ABCB1 Polymorphism on Levetiracetam Serum Concentrations in Epileptic Uygur Children in China.

Zhao Ting T   Yu Jing J   Wang Ting-Ting TT   Feng Jie J   Zhao Wen-Bo WB   Sun Li L   Yu Lu-Hai LH   Li Hong-Jian HJ   Sun Yan Y  

Therapeutic drug monitoring 20201201 6


<h4>Background</h4>Interindividual variations in the efficacy of antiseizure medications make epilepsy treatment challenging. This is due to genetic factors such as gene polymorphisms in Adenosine-triphosphate (ATP)-binding cassette sub-family B member 1 (ABCB1). In this article, the impact of polymorphisms in the P-glycoprotein-encoding gene, ABCB1 (C1236T, G2677T/A, and C3435T), on levetiracetam disposition was evaluated in Uygur Chinese children with epilepsy.<h4>Methods</h4>MDR1 C3435T polym  ...[more]

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