A Genetic Variant of the Serine Racemase Gene Is Associated with Schizophrenia

Yukitaka Morita, Hiroshi Ujike, Yuji Tanaka, Kyohei Otani, Makiko Kishimoto, Akiko Morio, Tatsuya Kotaka, Yuko Okahisa, Masayuki Matsushita, Akiko Morikawa, Kenji Hamase, Kiyoshi Zaitsu, Shigetoshi Kuroda

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79 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1200-1203
Number of pages4
JournalBiological Psychiatry
Volume61
Issue number10
DOIs
Publication statusPublished - May 15 2007

Keywords

  • Case-control study
  • column-switching high-performance liquid chromatography system
  • promoter activity
  • schizophrenia
  • serine racemase
  • single-nucleotide polymorphism

ASJC Scopus subject areas

  • Biological Psychiatry

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  • Cite this

    Morita, Y., Ujike, H., Tanaka, Y., Otani, K., Kishimoto, M., Morio, A., Kotaka, T., Okahisa, Y., Matsushita, M., Morikawa, A., Hamase, K., Zaitsu, K., & Kuroda, S. (2007). A Genetic Variant of the Serine Racemase Gene Is Associated with Schizophrenia. Biological Psychiatry, 61(10), 1200-1203. https://doi.org/10.1016/j.biopsych.2006.07.025