INFLUENCE OF THE SCN1A IVS5N + 5 G>A POLYMORPHISM ON THERAPY WITH CARBAMAZEPINE FOR EPILEPSY
Sterjev Z1,*, Kiteva G2, Cvetkovska E2, Petrov I2, Kuzmanovski I2, Ribarska TJ3, Nestorovska KA1, Matevska N1,Trajkovik-Jolevska S3, Dimovski AJ1, Suturkova, Lj1
*Corresponding Author: Zoran Sterjev, M. Sei. Pharm Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University “St. Cyril and Methodius,” str. Vodnjanska 17, 1000 Skopje, Republic of Macedonia; Tel./Fax:+38-923-120-229; E-mail: zost@ff.ukim.edu.mk
page: 19
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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 -subunit of the fi rst 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 -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, effi cacy and dose-dependence of CBZ therapy in 147 adult Macedonian patients and 137 non epileptic controls. No signifi cant 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 insignifi cant difference between patients with different genotypes, primarily due to a small number of patients.



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