Abstracts

Rationale: Clinical studies showed the role of neurotransmission modulated by dopamine (DA) in epilepsy. 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 3'- untranslated region (3'UTR) of the dopamine transporter gene (DAT1, NCBI Gene ID: 6531) and susceptibility to seizure development in TLE-HS. In addition, we intend to evaluate the possible association between this polymorphism and mood disorders. Methods: We assessed 117 patients with unequivocal TLE-HS, classified according to the criteria of the International League Against Epilepsy (ILAE, 2010) with and without psychiatric disorders (PD); 143 patients diagnosed with major depressive disorder (MDD) without epilepsy, and 108 healthy volunteers from general population with no personal or family history of epilepsy or PD. Individuals were assessed by a clinical interview held by SCID-I/P. Patients with other epileptic syndromes, with dual pathology or absence of lesion in MRI were excluded. Individuals were genotyped for the DAT1 3'UTR polymorphism by PCR amplification of the region of interest followed by capillary electrophoresis. 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: We found a higher frequency of 10 repeats homozygous genotype (10R/10R) in control group when compared to patients with TLE-HS with depression (p=0.028), but not in patients with TLE-HS without depression (p=0.553). Since the 10R allele was the most frequent, we tested if the presence of at least one such allele associates with the conditions studied here. There was a significant difference (p=0.009) in the frequency of 10R carriers between groups. Further analysis showed that there are fewer 10R carriers in the epilepsy group (22%), even higher when accompanied of depression (26%), when compared to either controls (10%, p=0.024, OR=3.09 [1.13, 8.5]) or MDD (10%, p=0.014, OR=2.99 [1.16, 7.60]). Conclusions: Our work suggests that the DAT 3'-UTR VNTR polymorphism is associated with TLE-HS, specially with depression as a comorbidity. The authors believe that the 10 repeats genotype might play a protective role for the development of TLE-HS with depression. Further studies with larger series are necessary to corroborate these findings. Funding: not applicable.