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

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Sterjev Z, Kiteva G, Cvetkovska E, Petrov I, Kuzmanovski I, Ribarska T, Nestorovska K, Matevska N, Trajkovik-Jolevska S, Dimovski A, Suturkova Lj

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

Balkan J Med Genet. 2012 Jun;15(1):19-24. doi: 10.2478/v10034-012-0003-1.

PubMed ID

24052718 [ View in PubMed

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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 alpha-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 alpha-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.

DrugBank Data that Cites this Article

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Carbamazepine	Sodium channel protein type 1 subunit alpha Gene symbol: SCN1A UniProt: P35498	---	(A;A) / (A;G)	IVS5N + 5 G>A (rs3812718)	Effect Directly Studied	Patients with this genotype have increased resistance to the anti-epileptic effects of carbamazepine.	Details