title: No evidence for association between a functional promoter variant of the Norepinephrine Transporter gene SLC6A2 and ADHD in a family-based sample.
abstract: Noradrenergic neurotransmission influences executive functions, attentional performance, and general alertness, involving neuronal networks affected in attention deficit/hyperactivity disorder (ADHD). The norepinephrine transporter facilitates the reuptake of norepinephrine and dopamine in the prefrontal cortex and represents the main target of atomoxetine, an effective drug in the treatment of ADHD. Due to its influence on catecholaminergic signaling, variants of the coding gene (SLC6A2) have been widely investigated in ADHD. Several previous studies report an association between single nucleotide polymorphisms located in SLC6A2 and ADHD; however, the findings are inconsistent. The variant A-3081T (rs28386840) has been shown to have major influence on the expression levels of SLC6A2 due to sequence alteration at a repressor binding site, with the T-allele being associated with ADHD. We tested this potential association of A-3081T in a German family-based ADHD sample of 235 children from 162 families, which has a power >99% based on the previously reported odds ratios. There was no evidence for an overtransmission of the risk allele T (transmission rate: 48.5%, P = 0.55). We conclude that A-3081T is not a major risk variant in our ADHD sample, though SLC6A2 remains an interesting candidate gene in ADHD, especially for the inattentive subtype.
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Germany. renner@kjp.uni-wuerzburg.de
authors: T J
authors: TJ
authors: Renner
authors: T T
authors: TT
authors: Nguyen
authors: M
authors: M
authors: Romanos
authors: S
authors: S
authors: Walitza
authors: C
authors: C
authors: Röser
authors: A
authors: A
authors: Reif
authors: H
authors: H
authors: Schäfer
authors: A
authors: A
authors: Warnke
authors: M
authors: M
authors: Gerlach
authors: K P
authors: KP
authors: Lesch
mesh_terms: D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human