A Genetic Polymorphism in the Promoter Region of DRD4 Associated with Expression and Schizophrenia

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.