A next‐generation sequencing–based pharmacogenetic study of ABCB1 , ABCC1 , and ABCC2 variants associated with antiseizure medication response in Turkish epilepsy patients

Abstract Objectives Epilepsy is a chronic neurological disorder characterized by a tendency to have recurrent seizures due to abnormal and excessive neuronal activity in the brain. Genetic variants in adenosine triphosphate (ATP)‐binding cassette (ABC) transporter genes, including ABCB1 , ABCC1 , and ABCC2 , may contribute to pharmacoresistance in epilepsy by altering the transport of anti‐seizure medications (ASMs) across the blood–brain barrier (BBB). This study aims to explore genetic polymorphisms in the ABCB1 , ABCC1 , and ABCC2 genes in Turkish epilepsy patients and to assess their impact on responsiveness to ASMs. Methods Targeted next‐generation sequencing was used for molecular genotyping of the ABCB1 , ABCC1 , and ABCC2 genes in genomic DNA from 35 patients. Results A total of nine common variants were analyzed in ABCB1 (rs2032582, rs1045642, rs1128503), ABCC1 (rs35626, rs212087, rs246221), and ABCC2 (rs717620, rs22773697, rs3740066). A statistically significant association was found between ABCB1 rs2032582:T>G and ASMs response in the recessive model (TT + TG vs. GG, p = 0.018, OR = 13.13; 95% CI: 1.69–160.1; Benjamini–Hochberg (BH) FDR‐adjusted q = 0.09), with the TT + TG genotypes being more frequent among drug‐responsive patients. Haplotype analysis showed that only the ABCB1 rs2032582 G allele was significantly more frequent in drug‐persistent patients compared with drug‐responsive patients (χ 2 = 3.916, p = 0.047). However, none of these associations remained statistically significant after false discovery rate (FDR) correction, and all findings should therefore be interpreted as exploratory. Significance The findings suggest that the ABCB1 rs2032582:T>G polymorphism may be associated with variability in treatment response among Turkish epilepsy patients. These results emphasize the potential involvement of ABC transporter–mediated drug efflux mechanisms in impacting the effectiveness of ASMs.