SCN1A and SCN1B gene polymorphisms and their association with plasma concentrations of carbamazepine and carbamazepine 10, 11 epoxide in Iranian epileptic patients. 2015

Soha Namazi, and Negar Azarpira, and Katayoon Javidnia, and Mehrdad Emami, and Rahimeh Rahjoo, and Razieh Berahmand, and Afshin Borhani-Haghighi
Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

From a genetic point of view, epilepsy is a polygenic multifactorial syndrome. The SCN1A and B genes belong to a family of genes that provide instructions for making sodium channels. Understanding the relevance of SCN1A and SCN1B gene polymorphisms to plasma concentration of carbamazepine (CBZ) and 'its active metabolite carbamazepine 10, 11 epoxide (CBZE), may shed more light on inter-individual variations in response to CBZ. METHODS In this cross-sectional study, genotype distribution and allele frequency of six non-synonymous exonic single nucleotide polymorphisms (SNPs) of the SCN1A and B genes were selected and determined using PCR-RFLP in 70 epileptic patients treated with CBZ for at least 6 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 SCN1A were found in 23, 37 and 10 patients, respectively. There were no statistically significant differences in the mean (± standard deviation) of plasma concentrations of CBZ (P=0.8) and CBZE (P=0.1) among these 3 groups. Likewise, there was no statistically significant relationship between SCN1A polymorphisms and CBZ concentration/dose ratio (P=0.7). A significant association was found between CBZ plasma level and CBZ concentration/dose with CBZ daily dose. All patients had the same genotype of SCN1B gene(CC). and no statistical analysis was performed. CONCLUSIONS No significant association between SCN1A gene polymorphisms and plasma levels of CBZ and CBZE were found[u1].

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