Polymorphisms in the dopamine D4 receptor gene and attention-deficit hyperactivity disorder

Neuroreport. 2003 Aug 6;14(11):1463-6. doi: 10.1097/00001756-200308060-00011.


There is considerable evidence to support a role of dopamine-related genes in the molecular aetiology of attention-deficit hyperactivity disorder (ADHD). A 48 bp repeat in exon three of the dopamine D4 receptor gene has been widely studied in clinical ADHD samples, and a meta-analysis of published studies suggests it is associated with ADHD. A number of other polymorphisms across this gene have been characterised but not so thoroughly investigated in relation to ADHD. In this study we have genotyped five polymorphisms (a 120 bp promoter-region duplication, the -616 C/G substitution, the -521 C/T substitution, a poly-G repeat in intron 1, and the 48 bp exon 3 repeat) across the gene in a large clinical sample (n = 188) and their families. We found that none of the markers is individually associated with ADHD, although there is evidence to suggest that a haplotype of markers in the 5' promoter region of the gene (allele 2 of the 120 bp duplication, the C allele of the -616 substitution, and the C allele of the -521 substitution) may confer susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Child
  • Chromosomes / genetics
  • DNA / genetics
  • Female
  • Gene Duplication
  • Genetic Linkage
  • Genetic Markers
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D4


  • DRD4 protein, human
  • Genetic Markers
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • DNA