Abstracts

Rationale: The role of dopamine (DA) in epilepsy is controversial. Pharmacological studies provide evidence that DA has anticonvulsant effects in limbic epilepsy. Additionally, there is biochemical evidence that dopaminergic dysfunction in the brain of people with epilepsy and animal models can be pro-convulsive. Despite the notion that multiple genetic factors predispose to epilepsy, there is evidence for a direct relationship between epilepsy and variations in genes encoding proteins involved in dopaminergic neurotransmission. In this study, we aimed to determine the possible association between a variable number tandem repeat (VNTR) polymorphism in the Intron 8 of the dopamine transporter gene (DAT1, NCBI Gene ID: 6531) and susceptibility to seizure frequency in temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS).  Methods: We assessed 119 patientswith unequivocal TLE-HS and 112 healthy volunteers. We assessed individuals by a clinical interview.We excluded Patients with other epileptic syndromes, dual pathology or absence of a lesion in MRI. In TLE-HS group, we evaluated epilepsy-related factors such as side of the lesion; the age of onset; duration of epilepsy; refractoriness; status epilepticus; febrile seizures, family history of epilepsy and psychiatric disorders; and other personal antecedents of note.  We genotyped individuals for the DAT Intron 8.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: No difference was observed between the TLE-HS and control group (p=0.395).We found a significant association between the presence of genotype homozygous for 6-repeats of the Intron 8 and seizure frequency (p=0.01). The frequency of the 6R / 6R genotype in the TLE-HS group was 42.6% in patients that had frequent (weekly/biweekly) seizures compared to patients with more sporadic seizures.  Conclusions: Our study suggests an association between DAT Intron 8associated with seizure frequency in TLE-HS. The authors believe that this polymorphism led to a lower DAT expression. This finding may suggest that the persistence of dopamine in the synapse is a predisposing factor to lower threshold and, consequently, more frequent seizures.  Funding: This work was supported by FAPESP - Foundation for the Support of Research in the State of Sao Paulo (grant number 2013/11361-4) and CAPES - Office for the Advancement of Higher Education. Dr. Valente is also supported by CNPq - National Council for Scientific and Technological Development (grant number 308968/2015-8).