Abstract
BackgroundEpilepsy is one of the most widely recognized neurological disorders; unfortunately, twenty to thirty percent of patients do not get cured from epilepsy, despite many trials of antiepileptic drug (AED) therapy. Immunotherapy may be a viable treatment strategy in a subset of epileptic patients. The association between Toll-like receptor polymorphisms and epilepsy clarifies the role of the immune system in epilepsy and its response to the drug. Thus, this study will focus on the relation between TLR4 rs1927914, rs11536858, rs1927911SNPs, and epilepsy in an Egyptian case-control study to assess their link to antiepileptic drug response.ResultsAccording to TLR4 rs1927914, there is a significant association between the SNP and the development of epilepsy, as CC genotype is 15.3 times more at risk for developing epilepsy than TT genotype, and CT is 11.1 times more at risk for developing epilepsy than TT. Also, patients with CC genotypes are 6.3 times more at risk for developing primary epilepsy than TT genotype.According to rs11536858, there is a significant association between cases and control groups, as AA genotypes are found to be more at risk for developing epilepsy than GG genotypes. Also, there is a statistically significant association between clonazepam resistance and rs11536858, as p value < 0.001* with the highest frequency of TT genotypes at 4.3%.According to rs1927911, there are no significant results between the cases and the control groups or between drug-responsive and drug resistance.ConclusionPossible involvement of the Toll-like receptor clarifies the importance of innate immunity in initiating seizures and making neuronal hyperexcitability. In this work, multiple significant associations between TLR SNPs and epilepsy, epileptic phenotype, and drug-resistant epilepsy have been found. More studies with bigger sample sizes and different techniques with different SNPs are recommended to find the proper immunotherapy for epilepsy instead of the treatment by antiepileptic drugs.
Highlights
Epilepsy is one of the most widely recognized neurological disorders; twenty to thirty percent of patients do not get cured from epilepsy, despite many trials of antiepileptic drug (AED) therapy
The capacity of ligand binding with Toll-like receptor 4 (TLR4) may be changed due to alteration in the signals caused by single-nucleotide polymorphisms (SNPs) in the extracellular domain of TLR4 which will alter the level of cytokines either pro- or anti-inflammatory cytokines and alter the susceptibility of chronic inflammation
The association between TLR genetic polymorphism rs1927914 and epilepsy types were presented in Table 4; a significant association was detected as p value was 0.001*, cases with CC genotype are more risky for developing primary epilepsy than TT cases by 6.3 times (OR = 6.3)
Summary
Epilepsy is one of the most widely recognized neurological disorders; twenty to thirty percent of patients do not get cured from epilepsy, despite many trials of antiepileptic drug (AED) therapy. The association between Tolllike receptor polymorphisms and epilepsy clarifies the role of the immune system in epilepsy and its response to the drug. Inflammatory cytokines and immune cells were reported to have a significant role in the initiation and relapse of epileptic seizures and the association of other diseases with epilepsy [1]. All data were collected from the Ensemble Genome Browser (www.ensembl.org). These SNPs rs1927911, rs1927914, and rs10759931 have not been previously studied in Egypt
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