title: SCN1A and SCN1B gene polymorphisms and their association with plasma concentrations of carbamazepine and carbamazepine 10, 11 epoxide in Iranian epileptic patients.
abstract: 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].
authors.affiliation: Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Soha
authors.initials: S
authors.lastname: Namazi
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Katayoon
authors.initials: K
authors.lastname: Javidnia
authors.affiliation: Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Emami
authors.affiliation: Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Rahimeh
authors.initials: R
authors.lastname: Rahjoo
authors.affiliation: Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Razieh
authors.initials: R
authors.lastname: Berahmand
authors.affiliation: Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Neurology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Borhani-Haghighi
keywords: Carbamazepine Carbamazepine 10-11-; Epilepsy; SCN1A; SCN1B; SNP; epoxide