SCN۱A and SCN۱B gene polymorphisms and their association with plasma concentrations of carbamazepine and carbamazepine ۱۰, ۱۱ epoxide in Iranian epileptic patients

Objective (s): From a genetic point of view, epilepsy is a polygenic multifactorial syndrome. The SCN۱A and B genes belong to a family of genes that provide instructions for making sodium channels. Understanding the relevance of SCN۱A and SCN۱B gene polymorphisms to plasma concentration of carbamazepine (CBZ) and its active metabolite carbamazepine ۱۰, ۱۱ epoxide (CBZE), may shed more light on inter-individual variations in response to CBZ. Materials and Methods: In this cross-sectional study, genotype distribution and  allele frequency of six non-synonymous exonic single nucleotide polymorphisms (SNPs) of the SCN۱A  and B genes were selected  and determined using PCR-RFLP in ۷۰ epileptic patients treated with CBZ for at least ۶ months. The patients had no hepatic or renal diseases and received no medications known to have a major interaction with CBZ. Serum concentrations of CBZ and CBZE were measured using High-Performance Liquid Chromatography (HPLC). Results: The AA, AG and GG alleles of SCN۱A were found in ۲۳, ۳۷ and ۱۰ patients, respectively. There were no statistically significant differences in the mean (± standard deviation) of plasma concentrations of CBZ (P=۰.۸) and CBZE (P=۰.۱) among these ۳ groups.  Likewise, there was no statistically significant relationship between SCN۱A polymorphisms and CBZ concentration/dose ratio (P=۰.۷). A significant association was found between CBZ plasma level and CBZ concentration/dose with CBZ daily dose. All patients had the same genotype of SCN۱B gene(CC). and no statistical analysis was performed. Conclusion: No significant association between SCN۱A gene polymorphisms and plasma levels of CBZ and CBZE were found.

Keywords:

Carbamazepine Carbamazepine ۱۰-۱۱- , epoxide , Epilepsy , SCN۱A , SCN۱B , SNP