Immunogenetic predisposing factors for mesial temporal lobe epilepsy with hippocampal sclerosis

被引:6
作者
Leal, Barbara [1 ,2 ]
Chaves, Joao [3 ]
Carvalho, Claudia [1 ,2 ]
Bettencourt, Andreia [1 ,2 ]
Brito, Claudia [2 ]
Boleixa, Daniela [2 ]
Freitas, Joel [3 ]
Bras, Sandra [2 ]
Lopes, Joao [4 ]
Ramalheira, Joao [4 ]
Costa, Paulo P. [1 ,5 ]
da Silva, Berta Martins [1 ,2 ]
da Silva, Antonio Martins [1 ,4 ]
机构
[1] Univ Porto, UMIB, ICBAS, Rua Jorge Viterbo Ferreira, Porto, Portugal
[2] UPorto, Lab Imunogenet, DPIM, ICBAS, Rua Jorge Viterbo Ferreira, Porto, Portugal
[3] Hosp Santo Antonio, Serv Neurol, Ctr Hosp Porto, Porto, Portugal
[4] Hosp Santo Antonio, Serv Neurofisiol, Ctr Hosp Porto, Porto, Portugal
[5] Inst Nacl Saude Dr Ricardo Jorge Porto, Dept Genet, Porto, Portugal
关键词
Epilepsy; genetics; neuroinflammation; cytokines; SNPs; MTLE-HS; JUVENILE MYOCLONIC EPILEPSY; HUMAN-LEUKOCYTE ANTIGENS; LENNOX-GASTAUT SYNDROME; CLASS-II ALLELES; INTERLEUKIN-1-BETA GENE; INFLAMMATORY CYTOKINES; TNF-ALPHA; RAT MODEL; ASSOCIATION; POLYMORPHISM;
D O I
10.1080/00207454.2017.1349122
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Purpose: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1 and TNF-, 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-1), rs1800629 (-308 G>A, TNF-) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population.Methods: We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 12.0years, age of onset = 13.6 10.3years, 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-1 levels produced by this genotype. High IL-1 levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.
引用
收藏
页码:305 / 310
页数:6
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