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.
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: Stephen F Traynelis; Lonnie P Wollmuth; Chris J McBain; Frank S Menniti; Katie M Vance; Kevin K Ogden; Kasper B Hansen; Hongjie Yuan; Scott J Myers; Ray Dingledine Journal: Pharmacol Rev Date: 2010-09 Impact factor: 25.468
Authors: Jeffrey A Lieberman; Frank P Bymaster; Herbert Y Meltzer; Ariel Y Deutch; Gary E Duncan; Christine E Marx; June R Aprille; Donard S Dwyer; Xin-Min Li; Sahebarao P Mahadik; Ronald S Duman; Joseph H Porter; Josephine S Modica-Napolitano; Samuel S Newton; John G Csernansky Journal: Pharmacol Rev Date: 2008-09 Impact factor: 25.468
Authors: Elin Grundberg; Tony Kwan; Bing Ge; Kevin C L Lam; Vonda Koka; Andreas Kindmark; Hans Mallmin; Joana Dias; Dominique J Verlaan; Manon Ouimet; Daniel Sinnett; Fernando Rivadeneira; Karol Estrada; Albert Hofman; Joyce M van Meurs; André Uitterlinden; Patrick Beaulieu; Alexandru Graziani; Eef Harmsen; Osten Ljunggren; Claes Ohlsson; Dan Mellström; Magnus K Karlsson; Olle Nilsson; Tomi Pastinen Journal: Genome Res Date: 2009-08-04 Impact factor: 9.043
Authors: Michiko Nakazato; Kenji Hashimoto; Ulrike Schmidt; Kate Tchanturia; Iain C Campbell; David A Collier; Masaomi Iyo; Janet Treasure Journal: Ann Gen Psychiatry Date: 2010-06-25 Impact factor: 3.455