title: Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels.
abstract: BACKGROUND
  We previously reported a reduction in serum levels of D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, in schizophrenia, supporting the hypofunction hypothesis of NMDA neurotransmission in schizophrenia. In this study, we examined the genetic roles of serine racemase (SRR), an enzyme catalyzing the formation of D-serine from L-serine, and D-amino-acid oxidase (DAO) in the susceptibility to schizophrenia and the regulation of serum D-serine levels.
  
  
  METHODS
  We determined the complete cDNA and genomic structures of SRR and performed mutation screening. Single nucleotide polymorphisms (SNPs) in SRR and DAO were tested for their association with schizophrenia in both case-control and family-based designs and for correlation with serum levels of D-serine.
  
  
  RESULTS
  Genomic analyses revealed that human brain SRR transcripts consist of four isoforms with one major species, which were derived from alternative use of various 5' end exons. Genetic association analyses showed no significant association between SRR/DAO and schizophrenia. We replicated the decreased serum D-serine levels in schizophrenia in the sample set, but D-serine levels did not correlate with SRR/DAO genotypes.
  
  
  CONCLUSIONS
  The SRR/DAO are not likely to be major genetic determinants in the development of schizophrenia or control of serum D-serine levels.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Hisako
authors.initials: H
authors.lastname: Ohba
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama-Shigeno
authors.forename: Manabu
authors.initials: M
authors.lastname: Toyoshima
authors.forename: Akira
authors.initials: A
authors.lastname: Okuno
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D001345:Autoradiography / Q000379:methods; D015152:Blotting, Northern / Q000379:methods; D010054:Brief Psychiatric Rating Scale; D016022:Case-Control Studies; D003605:D-Amino-Acid Oxidase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D019998:Racemases and Epimerases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics*; D012694:Serine / Q000097:blood*; D000099300:Serine Racemase
chemical_list: D003605:D-Amino-Acid Oxidase; D012333:RNA, Messenger; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase