A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia

Biochem Biophys Res Commun. 1999 May 10;258(2):292-5. doi: 10.1006/bbrc.1999.0630.


The human dopamine D4 receptor gene (DRD4) is an important candidate gene for schizophrenia. We identified a novel -521C>T polymorphism in the 5'-promoter region of DRD4. A transient expression method revealed that the T allele of this polymorphism reduces the transcriptional efficiency by 40% compared with the C allele. This polymorphism is of interest because of reported elevation of D4-like sites and DRD4 mRNA in the postmortem schizophrenic brain. The C allele frequency was significantly higher in 252 Japanese schizophrenics (0.48) than in 269 Japanese controls (0.41) (p = 0. 02) [odds ratio = 1.35 (95% confidence interval 1.05 - 1.72)]. Although the association is weak and should be considered tentative until other studies replicate it, this polymorphism provides a tool with the potential to examine whether DRD4 is related to susceptibility to and neuroleptic response in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Chloramphenicol O-Acetyltransferase / genetics
  • DNA Primers
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D4
  • Schizophrenia / genetics*


  • DNA Primers
  • DRD4 protein, human
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Chloramphenicol O-Acetyltransferase