Abstracts

Rationale: The ATP-binding cassette B1 (ABCB1) gene encodes P-glycoprotein, which is thought to transport various antiepileptic drugs. The efflux transporter P-glycoprotein limits both gastrointestinal absorption of drugs, as well drugs access to the blood brain barrier. The purpose of this study was to investigate the influence of ABCB1 polymorphisms on drug responsiveness in Japanese children with epilepsy. Methods: ABCB1 C1236T, C3435T, and C2677T/A polymorphisms were genotyped in 26 patients with idiopathic epilepsy treated with carbamazepine monotherapy. ABCB1 polymorphism genotypes were determined using TaqMan assays, and the relationship of the polymorphisms to the risk of drug-resistant side effects, as well as plasma drug concentrations, was estimated by a logistic regression analysis and Kruskal-Wallis test. Results: One fourth of the patients (15%) were classified as drug-resistant and 22 patients (85%) were identified as drug-responsive. The drug-resistant group contained significantly more males than females (p = 0.026). Additionally, age at the time of examination and age of epilepsy onset were significantly greater in the drug-resistant group (p = 0.048, p = 0.015, respectively). None of the demographic characteristics was significantly different amongst any of the genotypes, indicating that these characteristics did not influence drug plasma concentration. The C3435T CC genotype (wild-type) tended to be associated with high initial drug plasma concentrations (p = 0.08), while the GG genotype (homozygotes) had lower maintained plasma concentrations than the other two genotypes (p = 0.08); however, both findings were not statistically significant. When compared to drug-resistant patients, drug-responsive patients were significantly more likely to have TT genotypes than the other two C1236T genotypes (p = 0.0007). No statistically significant differences were detected for the investigated genotypes and alleles in ABCB1 gene polymorphisms between patients exhibiting drug side effects and those with no side effects. Conclusions: Our results indicated that the TT genotype of ABCB1 C1236T may influence CBZ responsiveness in Japanese children with epilepsy. Funding: None