title: Response to methylphenidate is not influenced by DAT1 polymorphisms in a sample of Brazilian adult patients with ADHD.
abstract: Several lines of evidence suggest a relevant role for the dopamine transporter (DAT1) gene not only as a susceptibility factor for attention-deficit hyperactivity disorder (ADHD), but also as a predictor of individual methylphenidate (MPH) response. Pharmacogenetic studies of MPH response in ADHD have mainly focused on the 40-bp variable number of tandem repeats (VNTR) in the 3' untranslated region (3'-UTR) of DAT1. Most studies were performed in samples of children and conflicting findings were obtained. Only two studies have assessed 3'-VNTR in samples of adults-one with positive and the other with negative findings. In the present study, we investigate three potentially relevant polymorphisms in DAT1 gene (-839 C > T; Int8 VNTR and 3'-VNTR), and their possible role in therapeutic response to MPH treatment in a sample of 171 Brazilian adults with ADHD. The diagnostic procedures followed the DSM-IV criteria and the outcome measures were the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. Drug response was assessed by both categorical and dimensional approaches. There was no effect of any DAT1 polymorphisms or haplotypes on MPH response. This is the second report demonstrating absence of differences in MPH response according to DAT1 genotypes in adults with ADHD. Although DAT protein is crucial for the effect of MPH, genetic variations in DAT1 gene probably do not have a significant clinical role in this sample of adults with ADHD.
authors.affiliation: Departament of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal:15053, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Verônica
authors.initials: V
authors.lastname: Contini
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Victor
authors.forename: Francine Z C
authors.initials: FZ
authors.lastname: Marques
authors.forename: Guilherme P
authors.initials: GP
authors.lastname: Bertuzzi
authors.forename: Carlos A I
authors.initials: CA
authors.lastname: Salgado
authors.forename: Katiane L
authors.initials: KL
authors.lastname: Silva
authors.forename: Nyvia O
authors.initials: NO
authors.lastname: Sousa
authors.forename: Eugenio H
authors.initials: EH
authors.lastname: Grevet
authors.forename: Paulo
authors.initials: P
authors.lastname: Belmonte-de-Abreu
authors.forename: Claiton H D
authors.initials: CH
authors.lastname: Bau
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics*; D001938:Brazil; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; C493214:SLC6A3 protein, human; D008774:Methylphenidate