Abstracts

Rationale: Mesial temporal lobe epilepsy (MTLE) is one of the most common and intractable forms of epilepsy showing a complex mode of inheritance. Previous studies have associated polymorphisms in pro-inflammatory cytokine interleukin 1-beta (IL1B) gene and increased predisposition to MTLE associated; however these findings are still controversial. In addition, we have found that the protein tyrosine phosphatase, receptor type, M gene (PTPRM) is up-regulated in brain tissue from patients with MTLE. PTPRM gene product regulates a variety of cellular processes including cell growth, differentiation and mitotic cycle. The aim of this study was to investigate if IL1B and PTPRM genes are associated with the phenotype in mesial temporal lobe epilepsy (MTLE). Methods: DNA samples were obtained from 203 unrelated patients with MTLE, as well as 204 unrelated controls, with no history of epilepsy. We selected five SNPs within IL1B and 110 SNPs within PTPRM from HapMap database. SNPs were genotyped using the SNPlexTM genotyping system (Applied Biosystems). Minor allele frequency (MAF>0.05), linkage disequilibrium (r^2^>0.8) and Hardy-Weinberg equilibrium (HWE pvalue>0.05) were estimated using the HAPLOVIEW software. Statistical analysis was performed by a logistic regression model with Bonferroni correction for multiple comparisons. Results: We found association between SNP rs3730364 in the IL1B gene and MTLE [p=1.4x10^(-14), OR=0.11; 95%CI: 0.06 - 0.21]. Furthermore, we found 11 SNPs in with PTPRM gene which were significantly associated with MTLE (rs727037, rs638251, rs671369, rs1443616, rs1016188, rs583909, rs565798, rs9807775, rs8087904, rs3786368, rs727027 and rs634438) [p=1.2x10^(-11), OR= 0.12; 95%CI: 0.07-0.24 for rs727027]. Conclusions: Our association study shows that there is a relationship between one SNP in the IL1B gene as well as several SNPs in the PTPRM gene and MTLE. However, none of these SNPs appear to be functional variants. Although much progress has been made in the characterization of genes for the monogenic and rare forms of epilepsy the common epilepsy syndromes, usually showing complex inheritance remain a major challenge for gene identification, our study hopes to shed some light into this area. Supported by FAPESP