title: Association of the dopamine transporter (SLC6A3/DAT1) gene 9-6 haplotype with adult ADHD.
abstract: ADHD is a neuropsychiatric disorder characterized by chronic hyperactivity, inattention and impulsivity, which affects about 5% of school-age children. ADHD persists into adulthood in at least 15% of cases. It is highly heritable and familial influences seem strongest for ADHD persisting into adulthood. However, most of the genetic research in ADHD has been carried out in children with the disorder. The gene that has received most attention in ADHD genetics is SLC6A3/DAT1 encoding the dopamine transporter. In the current study we attempted to replicate in adults with ADHD the reported association of a 10-6 SLC6A3-haplotype, formed by the 10-repeat allele of the variable number of tandem repeat (VNTR) polymorphism in the 3' untranslated region of the gene and the 6-repeat allele of the VNTR in intron 8 of the gene, with childhood ADHD. In addition, we wished to explore the role of a recently described VNTR in intron 3 of the gene. Two hundred sixteen patients and 528 controls were included in the study. We found a 9-6 SLC6A3-haplotype, rather than the 10-6 haplotype, to be associated with ADHD in adults. The intron 3 VNTR showed no association with adult ADHD. Our findings converge with earlier reports and suggest that age is an important factor to be taken into account when assessing the association of SLC6A3 with ADHD. If confirmed in other studies, the differential association of the gene with ADHD in children and in adults might imply that SLC6A3 plays a role in modulating the ADHD phenotype, rather than causing it.
authors.affiliation: Department of Psychiatry, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands. b.franke@antrg.umcn.nl
authors.forename: B
authors.initials: B
authors.lastname: Franke
authors.forename: M
authors.initials: M
authors.lastname: Hoogman
authors.forename: A
authors.initials: A
authors.lastname: Arias Vasquez
authors.forename: J G A M
authors.initials: JG
authors.lastname: Heister
authors.forename: P J
authors.initials: PJ
authors.lastname: Savelkoul
authors.forename: M
authors.initials: M
authors.lastname: Naber
authors.forename: H
authors.initials: H
authors.lastname: Scheffer
authors.forename: L A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: C C
authors.initials: CC
authors.lastname: Kan
authors.forename: J J S
authors.initials: JJ
authors.lastname: Kooij
authors.forename: J K
authors.initials: JK
authors.lastname: Buitelaar
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human