Identification of Multiple Serine Racemase (SRR) mRNA Isoforms and Genetic Analyses of SRR and DAO in Schizophrenia and d-Serine Levels
| Autor: | Masaomi Iyo, Kazuhiko Nakamura, Yoshimi Iwayama-Shigeno, Eiji Shimizu, Manabu Toyoshima, Masanari Itokawa, Kazuo Yamada, Kenji Hashimoto, Akira Okuno, Norio Mori, Tomoko Toyota, Hitomi Takao, Tetsuo Ohnishi, Takeo Yoshikawa, Hisako Ohba, Yoshio Minabe |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
D-Amino-Acid Oxidase Male Psychosis Genotype DNA Mutational Analysis Molecular Sequence Data Racemases and Epimerases Single-nucleotide polymorphism Biology medicine.disease_cause Polymorphism Single Nucleotide Linkage Disequilibrium Serine Gene Frequency medicine Brief Psychiatric Rating Scale Humans RNA Messenger Biological Psychiatry Genetic association Family Health Genetics Mutation Reverse Transcriptase Polymerase Chain Reaction Alternative splicing Genomics Middle Aged Blotting Northern medicine.disease Case-Control Studies Serine racemase Glycine Schizophrenia Autoradiography Female |
| Zdroj: | Biological Psychiatry. 57:1493-1503 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2005.03.018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect