In:
Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 6 ( 2020-12), p. 886-892
Abstract:
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 χ 2 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.
Type of Medium:
Online Resource
ISSN:
0163-4356
DOI:
10.1097/FTD.0000000000000805
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2020
detail.hit.zdb_id:
2048919-5
SSG:
15,3
