PTPRM and IL1B investigation in mesial temporal lobe epilepsy with hippocampal atrophy by SNP genotyping

Author(s)

Renato Oliveira dos Santos

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2010-08-30

Examining board members

Cláudia Vianna Maurer Morelli; Mônica Barbosa de Melo; Ângela Cristina do Valle

• Advisor: Íscia Teresinha Lopes Cendes; Cláudia Vianna Maurer Morelli

Abstract

Epilepsies are a group of chronic neurological disease characterized by seizures; an intermittent disorder of the nervous system caused by an abnormal and synchronized electrical discharge of the neurons. Mesial temporal lobe epilepsy (MTLE) is the most common form of epilepsy, representing approximately 30% of cases in adults and has the complex partial seizure as a typical manifestation. MTLE is frequently related with medically refractory seizures and the main symptoms are predominantly generated by medial temporal lobe structures. In fact, the relationship between MTLE and mesial temporal sclerosis (MTS) is well established, however the mechanisms responsible for this finding are poorly understood. Recently, genes linked to inflammatory processes, such as IL1B has been involved with MTLE in humans and in animal models. In addition, we have identified a differential expression in human hippocampi that were surgically extracted from refractory MTLE for the PTPRM gene. Since we had these observations, we investigated the association of the IL1B and PTPRM genes and MTLE associated with HS. One hundred seventy nine patients were selected from HC-UNICAMP and 24 patients from HC-USP Ribeirão Preto, diagnosed with MTLE with mangnetic resonance imaging (MRI) signs of MTS and 204 healthy individuals with no history of epilepsy, to compose the control group. To this study we employed the SNPlex system to genotype 119 SNPs in PTPRM gene and seven SNPs in the IL1B gene. Besides, one additional SNP in the IL1B gene was genotyped by PCR and enzymatic digestion. Twenty SNPs in the PTPRM gene and one SNP in the IL1B gene were found in association with the MTLE with MRI signs of MTS. Our association study shows that there is a relationship between IL1B as well PTPRM genes and MTLE. 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. In this way, our study hopes to shed some light into this area (AU)