Identification of a novel variant of the human NR2B gene promoter region and its possible association with schizophrenia
| Autor: | Ryosuke Miyatake, A. Furukawa, Hiroshi Suwaki |
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| Rok vydání: | 2002 |
| Předmět: |
Molecular Sequence Data
Pheochromocytoma Biology PC12 Cells Receptors N-Methyl-D-Aspartate Cellular and Molecular Neuroscience Plasmid Gene Frequency Genes Reporter Reference Values Animals Humans Luciferase Amino Acid Sequence Allele Molecular Biology Gene DNA Primers Podophyllotoxin Genetics Regulation of gene expression Binding Sites Podophyllin Base Sequence Genetic Variation Promoter Rats Up-Regulation Psychiatry and Mental health Nerve growth factor Gene Expression Regulation nervous system Schizophrenia Gene polymorphism 5' Untranslated Regions |
| Zdroj: | Molecular Psychiatry. 7:1101-1106 |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | N-methyl-D-aspartate (NMDA) receptor dysfunction is involved in the pathogenesis of schizophrenia. We determined the nucleotide sequence of the 5'-upstream region of the human NMDA receptor 2B (NR2B) subunit gene and identified a novel T-200G variant located in one of the Sp1 binding sites. To investigate the effect of this variant on the transcriptional activity of the hNR2B gene, we performed gene reporter assays using PC12 pheochromocytoma cells transiently transfected with luciferase reporter plasmids. In the absence of nerve growth factor (NGF), luciferase activities did not significantly differ between the two alleles and the control plasmid. However, luciferase reporter activity of the T allele was significantly up-regulated compared to that of the G allele in the presence of NGF (P = 0.0013), indicating that this polymorphic site is a critical region for NR2B gene regulation through NGF-induced Sp1-binding. A case control study showed that the frequency of the G allele (P = 0.0164) was significantly higher in 100 schizophrenics than in 100 controls. These findings suggest that the T-200G variant causes dysfunction of NMDA receptors consisting of the NR2B subunit and may be involved in the development of schizophrenia. Replication studies of independent samples and family-based association studies are necessary to further evaluate the significance of our findings. |
| Databáze: | OpenAIRE |
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