Abstracts

Rationale: Some epilepsy patients cite sensitivity (e.g. worsened seizures or side effects) to generic antiepileptic drug (AED) formulation compared to brand. In this exploratory study, we denote such patients as generic brittle (GB). The objective was to elucidate genes that differentiate GB patients from non-GB patients. Methods: Subjects were outpatients from an epilepsy clinic at the U of Maryland Medical Center. GB status for these patients was based on three factors: 1) history of either intractable seizures or AED adverse event(s); 2) opinion about generic brittleness in general or in their personal experience; 3) whether they were taking brand or generic AED. 24 single nucleotide polymorphisms (SNPs) and two copy number variants (CNVs) in 12 genes were genotyped in 148 subjects. Taqman assays were used to genotype SNPs and CNVs. Analyses included allele frequencies, Hardy-Weinberg equilibrium analysis, and comparison to all individuals in the 1000 Genomes Project Phase 3. Multiple comparisons were adjusted using Bonferroni adjustment. Results: Among the 148 subjects, 60 were GB (40.5%). The SCN1A: rs2298771 (p=0.051) and ABCC2:rs3740066 (p=0.048) showed some level of association in single SNP analysis, however did not pass the criteria of p Conclusions: No examined SNP or CNV was associated significantly with GB status. In a cohort comprised of nearly half GB epilepsy patients, the frequency of variant alleles did, however, differ from the general population. CYP3A5*3, notably, was found in all GB subjects with carbamazepine exposure. Results suggest that a study powered to detect rare variants may find gene associations for GB status. Funding: The BEEP2 Study was funded by FDA HHSF223201400188C.