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

• Published in: Biological psychiatry (1969) 2007-05, Vol.61 (10), p.1200-1203
• Main Authors: Morita, Yukitaka, Ujike, Hiroshi, Tanaka, Yuji, Otani, Kyohei, Kishimoto, Makiko, Morio, Akiko, Kotaka, Tatsuya, Okahisa, Yuko, Matsushita, Masayuki, Morikawa, Akiko, Hamase, Kenji, Zaitsu, Kiyoshi, Kuroda, Shigetoshi
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Alleles; Biological and medical sciences; Case–control study; column-switching high-performance liquid chromatography system; Female; Gene Expression - physiology; Genotype; Humans; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide - genetics; promoter activity; Promoter Regions, Genetic - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Racemases and Epimerases - genetics; Schizophrenia; Schizophrenia, Disorganized - diagnosis; Schizophrenia, Disorganized - genetics; Schizophrenia, Paranoid - diagnosis; Schizophrenia, Paranoid - genetics; Serine - blood; serine racemase; single-nucleotide polymorphism
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.07.025

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.