Abstracts

Rationale: Temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) is the most frequent cause of drug-resistant epilepsy in adults. Two polymorphisms in serotonin transporter gene (5-HTT), a 44 bp insertion/deletion in the 5regulatory region (5-HTTLPR) and a VNTR polymorphism in the second intron (5-HTTVNTR) modulate transcription. In this study, we aimed to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. Methods: We assessed 110 patients with unequivocal TLE-HS and 103 healthy volunteers. Individuals were assessed by a clinical interview held by SCID-I/P. Patients with other epileptic syndromes, dual pathology or absence of lesion in MRI were excluded. In TLE-HS group, we evaluated epilepsy-related factors such as: side of the lesion; age of onset; duration of epilepsy; refractoriness; status epilepticus; febrile seizures, family history of epilepsy in general and psychiatric disorders; and other personal antecedents of note. Individuals were genotyped for the 5HTT-LPR and 5HTT-VNTR. Categorical variables were compared between groups by the Chi-square test or Fisher's exact test, whereas numerical variables were compared by the Kruskal-Wallis test and Wilcoxon-Mann-Whitney test. Significance was set at p < 0.05. Results: 5-HTTLPR: No difference was observed between the TLE-HS and control group (p=0.287) There was no correlation between 5-HTTLPR and epilepsy-related factors. 5-HTTVNTR: We found a significant association between the presence of genotype homozygous for 12-repeats of 5-HTTVNTR and family history of epilepsy (p=0.020). No difference was observed between the TLE-HS and control group (p=0.174). Conclusions: Our work suggests that 5-HTTVNTR may be associated with the presence of family history of epilepsy in patients with TLE-HS. Genotypes homozygous for 12-repeats increase the expression of 5-HTT mRNA. This finding may suggest the presence of a subgroup of patients with familial predisposition for the occurrence of seizures due to a neuronal hyperexcitability state determined by the higher expression of 5-HTT. Further studies with larger series are necessary to corroborate these findings. Funding: This work was supported by FAPESP - Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Foundation for the Support of Research in the State of Sao Paulo - Project Grant number 2013/11361-4) and CAPES - Coordena磯 de Aperfei篡mento de Pessoal de Nivel Superior (Office for the Advancement of Higher Education - financial support to Juliana Alcantara and Silvia Vincentiis).