title: The norepinephrine transporter gene and attention-deficit hyperactivity disorder.
abstract: The adrenergic system plays a known role in attentional systems and a suspected causal role in attention-deficit hyperactivity disorder (ADHD), based on evidence from pharmacological interventions and animal models. The efficacy of the highly selective noradrenergic reuptake inhibitor, tomoxetine, in treating ADHD symptoms supports the system's role in ADHD and points to the norephinephrine transporter as a candidate gene. This study tested the gene for the norepinephrine transporter (NET1) as a susceptibility factor in ADHD using three polymorphisms located in exon 9, intron 9, and intron 13. We examined the inheritance of these polymorphisms in a sample of 122 families with a total of 155 children with ADHD identified through an ADHD proband. Use of the transmission disequilibrium test failed to show significant evidence for biased transmission of any of the alleles or the haplotypes of these polymorphisms. We further investigated this gene by screening the probands for five known amino acid variants to determine if they contributed to the ADHD phenotype but observed only one (Thr99Ile) in our sample. Since the frequency of this variant (1.8%) was similar to that previously reported in a control sample (2.2%), it is unlikely that this variant is related to the ADHD phenotype. Our results do not support the NET1 gene as a major genetic susceptibility factor in ADHD.
authors.affiliation: Department of Psychiatry and Division of Cellular and Molecular Biology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. cbarr@uhnres.utoronto.ca
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Barr
authors.forename: Jamie
authors.initials: J
authors.lastname: Kroft
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Karen
authors.initials: K
authors.lastname: Wigg
authors.forename: Wendy
authors.initials: W
authors.lastname: Roberts
authors.forename: Molly
authors.initials: M
authors.lastname: Malone
authors.forename: Abel
authors.initials: A
authors.lastname: Ickowicz
authors.forename: Russell
authors.initials: R
authors.lastname: Schachar
authors.forename: Rosemary
authors.initials: R
authors.lastname: Tannock
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017354:Point Mutation; D027981:Symporters / Q000235:genetics*
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D004247:DNA