Association between SCN1A polymorphism and carbamazepine-resistant epilepsy

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The SCN1A gene encodes the α subunit of the neuronal voltage-gated sodium channel, which is a target for carbamazepine and other antiepileptic drugs (AEDs). • Recent studies have demonstrated that a common polymorphism of SCN1A IVS5-91 G > A was associated with carbamazepine and phenytoin use in daily practice. • However, it has not been determined whether the polymorphism affects carbamazepine or other AED responsiveness. WHAT THIS STUDY ADDS • This study demonstrated a significant association between the SCN1A IVS5-91 AA genotype and carbamazepine-resistant epilepsy, while the AA genotype did not affect carbamazepine use. AIMS To establish whether the SCN1A IVS5-91 G > A polymorphism of the SCN1A gene, which encodes the neuronal sodium channel α subunit, affects responsivenss to the antiepileptic drugs (AEDS) carbamazepine and/or phenytoin. METHODS SCN1A IVS5-91 G > A polymorphism was genotyped in 228 Japanese epileptic patients treated with AEDs. The association between AED responsiveness and the polymorphism was estimated by logistic regression analysis, adjusting for clinical factors affecting the outcome of AED therapy. RESULTS The frequency of the AA genotype was significantly higher in carbamazepine-resistant patients (odds ratio, 2.7; 95% confidence interval (CI), 1.1, 7.1) and was insignificantly higher in AED-resistant patients. CONCLUSIONS This is the first report demonstrating an association between the SCN1A polymorphism and carbamazepine-resistant epilepsy.