title: Variation in the Serotonin Transporter Gene and Alcoholism: Risk and Response to Pharmacotherapy.
abstract: SLC6A4, the gene encoding the serotonin transporter protein (5-HTT), has been extensively examined as a risk factor for alcohol dependence (AD). More recently, variability in the transporter gene was identified to be a potential moderator of treatment response to serotonergic medications such as ondansetron and sertraline. There is an insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the SLC6A4, with the most common alleles being a 14-repeat short (S) allele and a 16-repeat long (L) allele. The S allele has often been associated with AD. By contrast, the L allele has been associated with pharmacological responsiveness in some individuals with AD. Differences in clinical phenotype may determine the utility of the 5-HTTLPR polymorphism as a moderator of pharmacological interventions for AD. We review the AD typology and disease onset in the context of pharmacogenetic and genomic studies that examine the utility of 5-HTTLPR in improving treatment outcomes.
authors: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada miles.thompson@utoronto.ca.
authors: Miles D
authors: MD
authors: Thompson
authors: Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
authors: George A
authors: GA
authors: Kenna
mesh_terms: D000437:Alcoholism / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D017294:Ondansetron / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D012702:Serotonin Antagonists / Q000627:therapeutic use; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017294:Ondansetron