title: A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers.
abstract: Topiramate, an anticonvulsant medication, is an efficacious treatment for alcohol dependence. To date, little is known about genetic moderators of side effects from topiramate. The objective of this study was to examine 3 single nucleotide polymorphisms (SNPs) of the glutamate receptor GluR5 gene (GRIK1) as predictors of topiramate-induced side effects in the context of a laboratory study of topiramate. Heavy drinkers (n=51, 19 women and 32 men), 75% of whom met criteria for an alcohol use disorder, completed a 5-week dose escalation schedule to a target dose of either 200 or 300 mg or matched placebo. The combined medication groups were compared with placebo-treated individuals for side effects at target dose. Analyses revealed that an SNP in intron 9 of the GRIK1 gene (rs2832407) was associated with the severity of topiramate-induced side effects and with serum levels of topiramate. Genes underlying glutamatergic neurotransmission, such as the GRIK1 gene, may help predict heterogeneity in topiramate-induced side effects. Future studies in larger samples are needed to more fully establish these preliminary findings.
authors.affiliation: Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA. lararay@psych.ucla.edu
authors.forename: Lara A
authors.initials: LA
authors.lastname: Ray
authors.forename: Robert
authors.initials: R
authors.lastname: Miranda
authors.forename: James
authors.initials: J
authors.lastname: MacKillop
authors.forename: John
authors.initials: J
authors.lastname: McGeary
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Tidey
authors.forename: Damaris J
authors.initials: DJ
authors.lastname: Rohsenow
authors.forename: Chad
authors.initials: C
authors.lastname: Gwaltney
authors.forename: Robert W
authors.initials: RW
authors.lastname: Swift
authors.forename: Peter M
authors.initials: PM
authors.lastname: Monti