title: A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia.
abstract: 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.
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D012559:Schizophrenia / Q000235:genetics*