<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>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 (<italic>p</italic> = 0.94278), or between CBZ-responsive and unresponsive patients (<italic>p</italic> = 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.</p></abstract>

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.

Influence of the SCN1A IVS5N + 5 G&gt;A Polymorphism on Therapy with Carbamazepine for Epilepsy

Institute for Pharmaceutical Chemistry, Faculty of Pharmacy, University "St. Cyril and Methodius, Skopje, Republic of Macedonia

Clinic of Neurology, Faculty of Medicine, University "St. Cyril and Methodius, Skopje, Republic of Macedonia

Institute for Pharmaceutical Analysis, Faculty of Pharmacy, University "St. Cyril and Methodius, Skopje, Republic of Macedonia

Balkan Journal of Medical Genetics

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...

Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy

Publié en ligne: 20 juil. 2012

Pages: 19 - 24

DOI: https://doi.org/10.2478/v10034-012-0003-1

Mots clés
Carbamazepine (CBZ), Epilepsy, Pharmacoresistant epilepsy, SCN1A polymorphism

This content is open access.

Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy

Publié en ligne: 20 juil. 2012

Pages: 19 - 24

DOI: https://doi.org/10.2478/v10034-012-0003-1

Mots clésCarbamazepine (CBZ), Epilepsy, Pharmacoresistant epilepsy, SCN1A polymorphism

This content is open access.

Mots clés
Carbamazepine (CBZ), Epilepsy, Pharmacoresistant epilepsy, SCN1A polymorphism