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Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy
Carbamazepine (CBZ) blocks neuronal sodium channels in a voltage- and frequency-dependent manner, delaying the recovery of the channels from the inactivated state, reducing the number of action potentials within a burst, and decreasing burst duration. The α-subunit of the first neuronal sodium chann...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Macedonian Science of Sciences and Arts
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776651/ https://www.ncbi.nlm.nih.gov/pubmed/24052718 http://dx.doi.org/10.2478/v10034-012-0003-1 |
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author | Sterjev, Z Kiteva, G Cvetkovska, E Petrov, I Kuzmanovski, I Ribarska, TJ Nestorovska, KA Matevska, N Trajkovik-Jolevska, S Dimovski, AJ Suturkova, Lj |
author_facet | Sterjev, Z Kiteva, G Cvetkovska, E Petrov, I Kuzmanovski, I Ribarska, TJ Nestorovska, KA Matevska, N Trajkovik-Jolevska, S Dimovski, AJ Suturkova, Lj |
author_sort | Sterjev, Z |
collection | PubMed |
description | Carbamazepine (CBZ) blocks neuronal sodium channels in a voltage- and frequency-dependent manner, delaying the recovery of the channels from the inactivated state, reducing the number of action potentials within a burst, and decreasing burst duration. The α-subunit of the first neuronal sodium channel (SCN1A) is a major gene in different epilepsies. A synonymous polymorphism (SCN1A IVS5N + 5 G>A or rs3812718) is common in exon 5 of this gene. Mutations in the α-unit of this gene are associated with CBZ-resistant epilepsy and a higher maintenance dose of CBZ. We have investigated the association of this single nucleotide polymorphism (SNP) and epilepsy, efficacy and dose-dependence of CBZ therapy in 147 adult Macedonian patients and 137 non epileptic controls. No significant differences in allelic frequencies and genotype distribution were found between patients and controls (p = 0.94278), or between CBZ-responsive and unresponsive patients (p = 0.55449). An association between the A allele and a higher maintenance dose in CBZ-responsive patients was detected. No statistical difference was found between the plasma levels of CBZ and genotype of patients receiving the same dose, indicating that the variant exerts its effect at the level of receptor responsiveness. The predictive value of pretreatment testing showed a minor insignificant difference between patients with different genotypes, primarily due to a small number of patients. |
format | Online Article Text |
id | pubmed-3776651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Macedonian Science of Sciences and Arts |
record_format | MEDLINE/PubMed |
spelling | pubmed-37766512013-09-19 Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy Sterjev, Z Kiteva, G Cvetkovska, E Petrov, I Kuzmanovski, I Ribarska, TJ Nestorovska, KA Matevska, N Trajkovik-Jolevska, S Dimovski, AJ Suturkova, Lj Balkan J Med Genet Original Article Carbamazepine (CBZ) blocks neuronal sodium channels in a voltage- and frequency-dependent manner, delaying the recovery of the channels from the inactivated state, reducing the number of action potentials within a burst, and decreasing burst duration. The α-subunit of the first neuronal sodium channel (SCN1A) is a major gene in different epilepsies. A synonymous polymorphism (SCN1A IVS5N + 5 G>A or rs3812718) is common in exon 5 of this gene. Mutations in the α-unit of this gene are associated with CBZ-resistant epilepsy and a higher maintenance dose of CBZ. We have investigated the association of this single nucleotide polymorphism (SNP) and epilepsy, efficacy and dose-dependence of CBZ therapy in 147 adult Macedonian patients and 137 non epileptic controls. No significant differences in allelic frequencies and genotype distribution were found between patients and controls (p = 0.94278), or between CBZ-responsive and unresponsive patients (p = 0.55449). An association between the A allele and a higher maintenance dose in CBZ-responsive patients was detected. No statistical difference was found between the plasma levels of CBZ and genotype of patients receiving the same dose, indicating that the variant exerts its effect at the level of receptor responsiveness. The predictive value of pretreatment testing showed a minor insignificant difference between patients with different genotypes, primarily due to a small number of patients. Macedonian Science of Sciences and Arts 2012-06 2012-07-20 /pmc/articles/PMC3776651/ /pubmed/24052718 http://dx.doi.org/10.2478/v10034-012-0003-1 Text en © Macedonian Academy of Sciences and Arts This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs license (http://creativecommons.org/licenses/by-nc-nd/3.0/), which means that the text may be used for non-commercial purposes, provided credit is given to the author. |
spellingShingle | Original Article Sterjev, Z Kiteva, G Cvetkovska, E Petrov, I Kuzmanovski, I Ribarska, TJ Nestorovska, KA Matevska, N Trajkovik-Jolevska, S Dimovski, AJ Suturkova, Lj Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy |
title | Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy |
title_full | Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy |
title_fullStr | Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy |
title_full_unstemmed | Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy |
title_short | Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy |
title_sort | influence of the scn1a ivs5n + 5 g>a polymorphism on therapy with carbamazepine for epilepsy |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776651/ https://www.ncbi.nlm.nih.gov/pubmed/24052718 http://dx.doi.org/10.2478/v10034-012-0003-1 |
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