title: Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes.
abstract: D-Serine is an endogenous coagonist that increases the opening of N-methyl-D-aspartate (NMDA)-type glutamate receptor channels. We previously reported a reduction of D-serine serum levels in schizophrenia, supporting the disease hypothesis of NMDA receptor-mediated hypo-neurotransmission. The serum levels of D-serine are thought to reflect brain d-serine content. It is important to understand whether there is a direct link between the altered D-serine levels and NMDA receptor expression in vivo or whether these are independent processes. Two polymorphisms are known to regulate the expression of NMDA receptor subunit genes: (GT)(n) (rs3219790) in the promoter region of the NR2A subunit gene (GRIN2A) and -200T > G (rs1019385) in the NR2B gene (GRIN2B). These polymorphisms are also reported to be associated with schizophrenia. Therefore, we examined the correlation between these two polymorphisms and d-serine serum levels in mentally healthy controls, schizophrenics and the combined group. We observed no significant genotype-phenotype correlations in any of the sample groups. However, analyses of larger sample numbers and the detection of additional polymorphisms that affect gene expression are needed before we can conclude that NMDA receptor expression and serum levels of d-serine, if involved in schizophrenia pathophysiology, are independent and additive events.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakajima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Hoshika
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012559:Schizophrenia / Q000097:blood / Q000235:genetics; D012694:Serine / Q000097:blood*; D013223:Statistics as Topic
chemical_list: D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C121001:NR2B NMDA receptor