title: SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis.
abstract: OBJECTIVE
  Approximately a third of newly diagnosed epilepsy patients do not respond to antiepileptic drugs (AEDs). Evidence suggests that low penetrance variants in the genes of drug targets such as voltage-gated sodium channels may be involved in drug responsiveness. To examine this hypothesis, we compared data from two epilepsy cohorts from Malaysia and Hong Kong, as well as a meta-analysis from published data.
  
  
  METHODS
  Genotype analysis of 39 polymorphisms located in the SCN1A, SCN2A and SCN3A genes was performed on 1504 epilepsy patients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was performed for pooled data of SCN1A rs3812718 and rs2298771, and SCN2A rs17183814 polymorphisms.
  
  
  RESULTS
  Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. This finding was supported by a meta-analysis for SCN1A rs3812718 and rs2298771, and for SCN2A rs17183814 polymorphisms.
  
  
  CONCLUSIONS
  Our comprehensive study suggests that common polymorphisms in SCN1A, SCN2A and SCN3A do not play major roles in influencing response to AEDs. Original submitted 11 March 2013; Revision submitted 31 May 2013.
authors.affiliation: Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. batoolsadat@yahoo.com
authors.forename: Batoul Sadat
authors.initials: BS
authors.lastname: Haerian
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
authors.forename: Patrick
authors.initials: P
authors.lastname: Kwan
authors.forename: Hui Jun
authors.initials: HJ
authors.lastname: Tan
authors.forename: Azman Ali
authors.initials: AA
authors.lastname: Raymond
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006723:Hong Kong; D006801:Humans; D007223:Infant; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics*; D062552:NAV1.3 Voltage-Gated Sodium Channel / Q000235:genetics*; D011110:Polymorphism, Genetic; D015222:Sodium Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; C568251:SCN2A protein, human; C424715:SCN3A protein, human; D015222:Sodium Channels