Abstracts

Rationale: Experimental and clinical studies have shown that serotonin (5-HT) levels modulate susceptibility to seizures (Bagdy et al.,2007). 5-HT has a complex neural communication system mediated by at least 14 subtypes of pre and post-synaptic receptors in various forms and subunits. Experimental and clinical studies showed that HTR1A and HTR2A are related to epileptogenesis (Bagdy et al , 2007;Lothe et al., 2008; Fonseca et al. 2015). The gene encoding the HTR1A contains a single nucleotide polymorphism (SNP) in the promoter region -C-1019G- that regulates gene expression and receptor binding potential. Presence of G allele of the C-1019G increases the expression of presynaptic auto-receptor but decreases the expression of postsynaptic receptor, decreasing serotoninergic transmission and increasing neuronal excitability. To date, only one study addressed a homogeneous group of patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) in order to investigate the role of a polymorphism in the 5HTT gene in prediction of a AED treatment response (Kauffman et al,2009). This study aimed to determine the possible association between C-1019G polymorphism (rs6295) with epileptogenesis and epilepsy-related factors in TLE-HS.Methods: We included patients with unequivocal TLE-HS and 70 age-, sex- and ethnic features-matched healthy subjects from general population. Patients and controls were genotyped for the C-1019G polymorphism in the 5HT1A gene using TaqMan allelic discrimination using real-time polymerase chain reaction (7500 Real-Time PCR System; Applied Biosystems). We evaluated epilepsy-related factors such as age of onset, seizure types and frequency status epilepticus, febrile seizures and other personal antecedents of note; refractoriness and side of the lesion (SEE TABLE 1). Statistical analysis was performed using one-way ANOVA or Student’s t-test for numerical clinical variables and Pearson’s chi-square for categorical clinical variables. Significance was set at p < 0.05.Results: 82 patients (39 [47.5%] with left MTLE-HS; 31 [37.8%] with right MTLE-HS and; 12 [14.7 %] with bilateral MTLE-HS) were included. The mean age was 39.8 years (SD + 12.6) and 56.0% were women. The genotype distribution of C-1019 G did not differ between TLE-HS patients and controls (p 0.310). We found a significant association with the presence of GG genotype and earlier onset of epilepsy compared with CC genotype (p 0.025). We also found an association between GG genotype and bilateral TLE-HS (p 0.033). Other clinical variables were not associated with any genotype.Conclusions: Our work suggests that 5-HT1A C-1019G polymorphism may be associated with some aspects of epilepsy, such as an earlier age of onset. Larger series are necessary to corroborate these findings.