title: The C/C genotype of the C957T polymorphism of the dopamine D2 receptor is associated with schizophrenia.
abstract: The T allele of the human dopamine D2 receptor (DRD2) gene C957T polymorphism is associated with reduced mRNA translation and stability. This results in decreased dopamine induced DRD2 upregulation and decreased in vivo D2 dopamine binding. Conversely, the C allele of the C957T polymorphism is not associated with such changes in mRNA leading to increased DRD2 expression. PET and postmortem binding studies show that schizophrenia is often associated with increased DRD2 availability. We report that on the basis of comparing the frequencies of the C/C and T/T genotypes of 153 patients with schizophrenia and 148 controls that schizophrenia is associated with the C/C genotype. The C957T shows a population attributable risk for schizophrenia of 24% and an attributable risk in those with schizophrenia of 42%. Increased expression of D2 receptors associated with the C allele is likely to be important in the underlying pathophysiology of at least some forms of schizophrenia. Enhanced understanding of schizophrenia afforded by this finding may lead to advances in treatment and prevention.
authors.affiliation: Division of Mental Health, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Brisbane, Queensland 4029, Australia. bruce_lawford@health.qld.gov.au
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Lawford
authors.forename: Ross McD
authors.initials: RM
authors.lastname: Young
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Swagell
authors.forename: Mark
authors.initials: M
authors.lastname: Barnes
authors.forename: Simon C
authors.initials: SC
authors.lastname: Burton
authors.forename: Warren K
authors.initials: WK
authors.lastname: Ward
authors.forename: Karen R
authors.initials: KR
authors.lastname: Heslop
authors.forename: Susan
authors.initials: S
authors.lastname: Shadforth
authors.forename: Angela
authors.initials: A
authors.lastname: van Daal
authors.forename: C Phillip
authors.initials: CP
authors.lastname: Morris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001665:Binding Sites; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D049268:Positron-Emission Tomography; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2