Abstracts

Rationale: Experimental and clinical studies showed that reduction of serotonin (5HT) concentration in the brain enhance susceptibility to seizures. Serotoninergic neurotransmission have an important role in the neurobiology of epilepsy. Genetic variants which encode proteins related to serotonergic neurotransmission may regulate the levels of 5HT. An upstream variable number of tandem repeats polymorphism in monoamine oxidase A (MAOA) gene (MAOA-uVNTR) affect transcriptional efficiency of the MAOA promoter and MAOA enzyme activity. To date, only one study addressed the role of a polymorphism in the serotonin transporter gene (5HTT) in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) in order to predict AED response. We aimed to: (i) determine the possible association between MAOA uVNTR polymorphism and susceptibility to develop seizures in TLE-HS and (ii) evaluate the possible association between this variant and epilepsy-related factors in TLE-HS. Methods: We assessed 110 patients with unequivocal TLE-HS classified according to the criteria of the International League Against Epilepsy (ILAE, 2010) and 103 healthy volunteers from general population with no personal or family history of epilepsy or psychiatric disorders. Patients with other epileptic syndromes, with dual pathology or absence of lesion in MRI were excluded. We evaluated epilepsy-related factors such as side of the lesion, age of onset, duration of epilepsy, seizure types and frequency, refractoriness, status epilepticus, febrile seizures and other personal antecedents of note. Individuals were genotyped for the MAOA-uVNTR polymorphism by PCR amplification of the region of interest and using capillary electrophoresis system (Fragment AnalyzerTM). 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. Since the MAOA gene is located in the X chromosome, we used the classification of Sabol et al.(1) and Caspi et al.(2) to designate alleles as either low or high activity. We grouped apart female who were heterozygous. Significance was set at p < 0.05. Results: We found a significant association between the presence of high activity alleles of MAOA uVNTR and occurrence of daily and weekly seizures (p=0.026). However, we also found a negative correlation between high activity alleles and presence of GTC seizures (p=0.027). No other difference was observed between the TLE-HS and control group. Conclusions: Our work suggests that genetic polymorphism of the MAOA uVNTR is related to epilepsy severity, considering seizure frequency. One possible explanation for the negative correlation with GTCS is that an increase in the concentration and/or activity of MAOA could be a facilitatory mechanism for focal seizures, but not for the spreading of this activity. Further studies with larger series are necessary to corroborate these findings. References 1.Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 1998; 103:273?"9. 2.Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, et al. Role of genotype in the cycle of violence in maltreated children. Science. 2002; 297:851?"4. 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).