TY - JOUR
T1 - A Genetic Variant of the Serine Racemase Gene Is Associated with Schizophrenia
AU - Morita, Yukitaka
AU - Ujike, Hiroshi
AU - Tanaka, Yuji
AU - Otani, Kyohei
AU - Kishimoto, Makiko
AU - Morio, Akiko
AU - Kotaka, Tatsuya
AU - Okahisa, Yuko
AU - Matsushita, Masayuki
AU - Morikawa, Akiko
AU - Hamase, Kenji
AU - Zaitsu, Kiyoshi
AU - Kuroda, Shigetoshi
N1 - Funding Information:
This work was supported in part by grants from the Zikei Institute of Psychiatry (Okayama, Japan); the Ministry of Health, Labour, and Welfare of Japan; and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - 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.
AB - 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.
KW - Case-control study
KW - column-switching high-performance liquid chromatography system
KW - promoter activity
KW - schizophrenia
KW - serine racemase
KW - single-nucleotide polymorphism
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U2 - 10.1016/j.biopsych.2006.07.025
DO - 10.1016/j.biopsych.2006.07.025
M3 - Article
C2 - 17067558
AN - SCOPUS:34247596490
SN - 0006-3223
VL - 61
SP - 1200
EP - 1203
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 10
ER -