Association analysis of glycine- and serine-related genes in a Japanese population of patients with schizophrenia.
Differences in the levels of the glutamate-related amino acids glycine and serine in brain/plasma between schizophrenic patients and normal subjects and changes in the plasma concentrations of these amino acids according to the clinical course have been reported. It has been hypothesized that glycine and serine metabolism may be altered in schizophrenia. In fact, some genes related to the metabolism of these amino acids have been suggested to be candidate genes for schizophrenia. Thus, we performed a genomic case-control analysis of amino acid metabolism-related genes in Japanese patients with schizophrenia. Case-control genetic association analysis of PHGDH, SHMT1, SRR, and DAO was performed. In addition, the effect of the various genotypes resulting from these four genes on changes in plasma amino acid levels in schizophrenia was assessed. The genetic case-control analysis showed that no individual single-nucleotide polymorphism (SNP) in any of the four genes was associated with schizophrenia; only the two (rs3918347-rs4964770, P=0.0009) and three (rs3825251-rs3918347-rs4964770, P=0.002) SNP-based haplotype analysis of the DAO gene showed an association with schizophrenia even after correction for multiple testing. None of the genotypes studied was associated with changes in the plasma glycine and l- and d-serine levels during the schizophrenic clinical course. The DAO gene may be a susceptibility locus for schizophrenia.
Ohnuma
Tohru
T
Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan. tohru.oonuma@nifty.ne.jp
Shibata
Nobuto
N
Maeshima
Hitoshi
H
Baba
Hajime
H
Hatano
Tokiko
T
Hanzawa
Ryo
R
Arai
Heii
H
D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003605:D-Amino-Acid Oxidase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005998:Glycine / Q000097:blood; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000208:ethnology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019998:Racemases and Epimerases / Q000235:genetics*; D012559:Schizophrenia / Q000097:blood / Q000235:genetics*; D012694:Serine / Q000097:blood; D055815:Young Adult; D000099300:Serine Racemase
D003605:D-Amino-Acid Oxidase; D005998:Glycine; D012696:Glycine Hydroxymethyltransferase; D050543:Phosphoglycerate Dehydrogenase; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase; C417983:DAO protein, human; C520541:SHMT protein, human