Author(s):
Leal, Bárbara ; Chaves, João ; Carvalho, Cláudia ; Bettencourt, Andreia ; Brito, Cláudia ; Boleixa, Daniela ; Freitas, Joel ; Brás, Sandra ; Lopes, João ; Ramalheira, João ; Costa, Paulo ; Silva, Berta ; Martins Da Silva, António
Date: 2018
Persistent ID: http://hdl.handle.net/10400.18/6258
Origin: Repositório Científico do Instituto Nacional de Saúde
Subject(s): Adolescent; Adult; Aged; Case-Control Studies; Epilepsy, Temporal Lobe; Female; Genotype; HLA-DRB1 Chains; Hippocampus; Humans; Immunogenetics; Interleukin-1alpha; Male; Middle Aged; Polymorphism, Single Nucleotide; Sclerosis; Tumor Necrosis Factor-alpha; Young Adult; Causality; Determinantes da Saúde e da Doença; Doenças Genéticas
Description
Purpose: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1β and TNF-α, in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with febrile seizures (FS) and MTLE-HS development. The human leukocyte antigen (HLA) system has also been implicated in diverse epileptic entities, suggesting a variable role of this system in epilepsy. Our aim was to analyse the association between immunogenetic factors and MTLE-HS development. For that rs16944 (-511 T>C, IL-1β), rs1800629 (-308 G>A, TNF-α) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population. Methods: We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 ± 12.0 years, age of onset = 13.6 ± 10.3 years, 104 with FS antecedents) and 282 healthy controls in a case–control study. Results: The frequency of rs16944 TT genotype was higher in MTLE-HS patients compared to controls (14.9% in MTLE-HS vs. 7.7% in controls, p = 0.021, OR [95% CI] = 2.20 [1.13–4.30]). This association was independent of FS antecedents. No association was observed between rs1800629 genotypes or HLA-DRB1 alleles and MTLE-HS susceptibility. Also, no correlation was observed between the studied polymorphisms and disease age of onset. Conclusion: The rs16944 TT genotype is associated with MTLE-HS development what may be explained by the higher IL-1β levels produced by this genotype. High IL-1β levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.
