Abstract / Summary
Background Epilepsy affects millions of people worldwide, and drug-resistant epilepsy (DRE) poses significant challenges. This investigation examined the relationship between ABCB1 gene variations and the efficacy of levetiracetam (LEV) in patients with focal epilepsy. Materials and Methods We classified 360 focal epilepsy patients treated with LEV as responders to LEV (n=142), second ASM (n=92), or non-responders (n=126). Five ABCB1 polymorphisms (rs1128503, rs2032582, rs1045642, rs2235035, and rs1922242) were genotyped using TaqMan assays. ABCB1 gene expression was analyzed in whole blood samples from 73 patients. Statistical analyses compared genotype, allele, and haplotype distributions between the two groups using Fisher's exact test and evaluated mean ABCB1 gene expression levels across genotypes with a t-test or analysis of variance. Results Significant genetic associations were identified between the rs2235035 and rs1922242 polymorphisms and the response to LEV or followed by the second ASM. The minor alleles and mutant genotypes of both SNPs were more prevalent among responders, suggesting protective effects against DRE. The 'AAAAT' and GCGAT haplotypes were associated with improved treatment response. Blood samples investigation revealed increased ABCB1 expression in reference genotypes of rs2235035 and rs1922242 compared to heterozygotes. This study identified novel associations between ABCB1 polymorphisms (rs2235035, rs1922242) and LEV response in patients with focal epilepsy. Conclusions The findings suggest potential genetic markers for predicting treatment outcomes and provide insights into the functional implications of these polymorphisms. Additional studies are warranted to confirm these findings and investigate their potential use in individualized treatment of epilepsy.