The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in children
Abstract Background Epilepsy 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 epile...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-12-01
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| Series: | Egyptian Journal of Medical Human Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43042-020-00102-3 |
| _version_ | 1819078154150477824 |
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| author | Maha Abdelsalam Dina Salama Abd Elmagid Hend Magdy Amr Mohamed El-Sabbagh Maged Mostafa |
| author_facet | Maha Abdelsalam Dina Salama Abd Elmagid Hend Magdy Amr Mohamed El-Sabbagh Maged Mostafa |
| author_sort | Maha Abdelsalam |
| collection | DOAJ |
| description | Abstract Background Epilepsy 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. Results According 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. Conclusion Possible 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. |
| first_indexed | 2024-12-21T19:08:35Z |
| format | Article |
| id | doaj.art-7a7f6e19280441738fcf3f717c8525e8 |
| institution | Directory Open Access Journal |
| issn | 2090-2441 |
| language | English |
| last_indexed | 2024-12-21T19:08:35Z |
| publishDate | 2020-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj.art-7a7f6e19280441738fcf3f717c8525e82022-12-21T18:53:16ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412020-12-012111810.1186/s43042-020-00102-3The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in childrenMaha Abdelsalam0Dina Salama Abd Elmagid1Hend Magdy2Amr Mohamed El-Sabbagh3Maged Mostafa4Immunology Unit, Clinical Pathology Department, Faculty of Medicine, Mansura UniversityDepartment of Pediatrics, Faculty of Medicine, Mansoura UniversityPublic Health & Community Medicine Department, Faculty of medicine, Mansura UniversityMedical Microbiology and Immunology Department, Faculty of Medicine, Mansura UniversityImmunology Unit, Clinical Pathology Department, Faculty of Medicine, Mansura UniversityAbstract Background Epilepsy 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. Results According 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. Conclusion Possible 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.https://doi.org/10.1186/s43042-020-00102-3Antiepileptic drug-resistantEgyptianInnate immunityPCRPediatricRFLP |
| spellingShingle | Maha Abdelsalam Dina Salama Abd Elmagid Hend Magdy Amr Mohamed El-Sabbagh Maged Mostafa The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in children Egyptian Journal of Medical Human Genetics Antiepileptic drug-resistant Egyptian Innate immunity PCR Pediatric RFLP |
| title | The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in children |
| title_full | The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in children |
| title_fullStr | The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in children |
| title_full_unstemmed | The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in children |
| title_short | The association between toll-like receptor 4 (TLR4) genotyping and the risk of epilepsy in children |
| title_sort | association between toll like receptor 4 tlr4 genotyping and the risk of epilepsy in children |
| topic | Antiepileptic drug-resistant Egyptian Innate immunity PCR Pediatric RFLP |
| url | https://doi.org/10.1186/s43042-020-00102-3 |
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