ABCB1 Gene Polymorphisms Are Closely Associated With Drug-Resistant Epilepsy: Evidence Based on 377 Subjects in Chinese Pediatric Patients

Clin Neuropharmacol. 2023 Jun 7. doi: 10.1097/WNF.0000000000000555. Online ahead of print.

Abstract

Objective: P-glycoprotein plays a role in drug resistance of epileptic patients by limiting gastrointestinal absorption and brain access to antiseizure medications. This study aimed to evaluate the association between ABCB1 polymorphisms and drug resistance in epileptic pediatric patients.

Methods: Three hundred seventy-seven epileptic pediatric patients were treated with antiseizure medications and subsequently divided into the drug-responsive group (n = 256, 68%) and drug-resistant group (n = 121, 32%). The genomic DNA of patients in the different groups was extracted, followed by the determination of the ABCB1 gene polymorphisms using polymerase chain reaction-fluorescence staining in situ hybridization.

Results: Drug-resistant patients significantly exhibited a combined generalized and focal onset than drug-responsive patients (χ2 = 12.278, P < 0.001). The TT (χ2 = 5.776, P = 0.016) genotypes of G2677T and CT (χ2 = 6.165, P = 0.013) and TT (χ2 = 11.121, P = 0.001) genotypes of C3435T were significantly more frequent in drug-resistant patients than drug-responsive patients. Similarly, the GT-CT diplotype was significantly more frequent in drug-resistant patients than in drug-responsive patients.

Conclusion: Our study findings suggest that the ABCB1 G2677T and C3435T polymorphisms are significantly associated with drug resistance in epileptic patients.