title: A genetic variant of the serine racemase gene is associated with schizophrenia.
abstract: BACKGROUND
  Serine racemase (SRR) is a brain-enriched enzyme that converts L-serine to D-serine, which acts as an endogenous ligand of N-methyl D-aspartate (NMDA) receptors. Dysfunction of SRR may reduce the function of NMDA receptors and susceptibility to schizophrenia.
  
  
  METHODS
  We genotyped three single-nucleotide polymorphisms (SNPs) of the 5' region of the SRR gene in 525 patients with schizophrenia and 524 healthy controls. Effects of SNPs on the promoter activity and on serum levels of total and D-serine were examined.
  
  
  RESULTS
  We found a significant excess of the IVS1a+465C allele of the SRR gene in schizophrenia, especially in the paranoid subtype (p = .0028). A reporter assay showed that the IVS1a+465C allele had 60% lower promoter activity than did the IVS1a+465G allele.
  
  
  CONCLUSIONS
  The IVS1a+465C allele of the SRR gene, which reduces expression of the gene, is a risk factor for schizophrenia, especially the paranoid subtype.
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kyohei
authors.initials: K
authors.lastname: Otani
authors.forename: Makiko
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Morio
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kotaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okahisa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Akiko
authors.initials: A
authors.lastname: Morikawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamase
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Zaitsu
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019998:Racemases and Epimerases / Q000235:genetics*; D012562:Schizophrenia, Disorganized / Q000175:diagnosis / Q000235:genetics*; D012563:Schizophrenia, Paranoid / Q000175:diagnosis / Q000235:genetics*; D012694:Serine / Q000097:blood; D000099300:Serine Racemase
chemical_list: D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase