title: SCN1A variations and response to multiple antiepileptic drugs.
abstract: In the current study, we have used the haplotype-tagging single-nucleotide polymorphisms (SNPs) to determine associations between genetic variants in SCN1A and treatment response in 519 Caucasian patients with known response status for epilepsy treated with antiepileptic drugs (AEDs) with sodium channel blocking effects. Nine SNPs within SCN1A were genotyped in this cohort. The only association observed was for rs10188577. A greater proportion of drug-resistant patients were heterozygous compared with drug responsive patients (48.3% vs 35.4%, P=0.014). After correction for potential confounding factors, the association for rs10188577 was only marginally significant (P=0.049). In light of our findings, it seems unlikely that rs10188577 could be a major determinant of response to AEDs. However, looking at the influence of rs10188577 on the expressed quantitative trait association patterns within the immediate vicinity of SCN1A, we found significant associations with neighbouring sodium channel genes, SCN7A and SCN9A (P<0.025), which warrants further studies.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: T S C
authors.initials: TS
authors.lastname: Yip
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: C
authors.initials: C
authors.lastname: O'Doherty
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore.
authors.forename: N C K
authors.identifier: 0000000292135572
authors.initials: NC
authors.lastname: Tan
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: L M
authors.initials: LM
authors.lastname: Dibbens
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Suppiah
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human