A genetic variant of the serine racemase gene is associated with schizophrenia.
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.
Morita
Yukitaka
Y
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ujike
Hiroshi
H
Tanaka
Yuji
Y
Otani
Kyohei
K
Kishimoto
Makiko
M
Morio
Akiko
A
Kotaka
Tatsuya
T
Okahisa
Yuko
Y
Matsushita
Masayuki
M
Morikawa
Akiko
A
Hamase
Kenji
K
Zaitsu
Kiyoshi
K
Kuroda
Shigetoshi
S
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
D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase