Abstracts

Rationale: Mesial temporal lobe epilepsy (MTLE) is associated with the highest proportion of the drug-resistant patients. One hypothesis to explain differences in drug response in epilepsy treatment is the association with pharmacogenetic differences present in genes related to drug-metabolism and ion channels. Therefore, allelic variations in these genes could be responsible for degreased efficiency of antiepileptic drugs and failure to control seizures. The purpose of this study was to investigate whether single nucleotide polymorphisms (SNPs) on drug-transporter genes (ATP-binding cassette family: ABCB1, ABCC2, ABCC4; and RLIP76-ralA-binding-protein1) and ion channels (SCN11A–Na+channel α subunit; CACNA1B–Ca+2channel α1B subunit) could be associated with pharmacoresistance in a large group of MTLE patients. Methods: We chose 11 validated SNPs in dbSNPs database: rs12680, rs 12454987, rs8092935 (RALBP1); rs2235039, rs282564, rs2229109, rs3213619 (ABCB1); 2273697(ABCC2); 2274407(ABCC4); 2298771(SCN11A); 4422842(CACNA1B). Genotyping was carried out using the TaqMan system™(Applied Biosystems). We included 90 drug-resistant MTLE patients and compared with 60 drug-responsive MTLE patients.Results: Genotypic frequencies were in Hard-Weinberg equilibrium in both groups and no significant allelic differences were observed, for any of the SNPs tested, between the two groups (p>0.01). In addition, no differences were found between the allelic frequencies in both groups and the NCBI SNPs database.Conclusions: In conclusion, we found a lack of correlation between SNPs in candidate genes associated with drug-metabolism and ion channels and pharmacoresistance in MTLE.