A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder

Mol Psychiatry. 2000 Sep;5(5):523-30. doi: 10.1038/sj.mp.4000751.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition of early childhood onset characterised by marked inattention, hyperactivity and impulsiveness. Molecular genetic investigations of ADHD have found positive associations with the 480-bp allele of a VNTR situated in the 3' untranslated region of DAT1 and allele 7 of a VNTR in exon 3 of DRD4. A number of independent studies have attempted to replicate these findings but the results have been inconsistent. We used both family-based and case control approaches to examine these polymorphisms in a sample of 137 children diagnosed with ICD-10, DSM-IV or DSM-III-R ADHD. We found no evidence of association with the DAT1 polymorphism, despite a sample size that has up to 80% power to detect a previously reported effect size. We observed a significant increase in the DRD4 7 repeat allele amongst ADHD probands (21.7%) and their parents (18.9% in mothers, 22.3% in fathers), compared to ethnically matched controls (12.8%). However TDT analysis showed no preferential transmission of allele 7 to ADHD probands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Child
  • Dopamine Plasma Membrane Transport Proteins
  • Family Health*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Phenotype
  • Polymorphism, Genetic
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D4

Substances

  • Carrier Proteins
  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • Receptors, Dopamine D4