Association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia

Begni, Silvia; Moraschi, Stefania; Bignotti, Stefano; Fumagalli, Fabio; Rillosi, Luciana; Pérez, Jorge; Gennarelli, Massimo

doi:10.1016/s0006-3223(02)01783-3

Cited by 58 publications

(39 citation statements)

References 12 publications

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“…In addition we show that inhibition of NFκB by SN50 can attenuate the ATRA dependent increase in NMDAR1, a well known marker of neuronal differentiation. Previous reports suggest that NMDAR1 is regulated by NFκB, AP-1, CREB, and SP-1 elements in the promoter region of the human gene [36][37][38][39]. Taken together these results allow speculation that ATRA mediated differentiation involves pathways which are sensitive to cellular redox status.…”

Section: Discussionmentioning

confidence: 58%

All-trans-retinoic acid induces manganese superoxide dismutase in human neuroblastoma through NF-κB

Kiningham

Cardozo

Cook

et al. 2008

Free Radical Biology and Medicine

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Retinoids are signaling molecules that are involved in proliferation, differentiation and apoptosis during development. Retinoids exert their effects, in part, by binding to nuclear receptors, thereby altering gene expression. Clinical use of retinoids in the treatment of neuroblastoma is of interest due to their success in management of acute promyelocytic leukemia. Using the SK-N-SH human neuroblastoma cell line we investigated the effect of the differentiation agent, all-trans-retinoic acid (ATRA) on manganese superoxide dismutase (MnSOD) expression, an enzyme previously shown to enhance differentiation in vitro. Manganese superoxide dismutase mRNA, protein and activity levels increased in a time dependent manner upon treatment with ATRA. Nuclear levels of the NFκB proteins, p50 and p65, increased within 24 h of ATRA administration. This increase paralleled the degradation of the cytoplasmic inhibitor, IκB-β. Furthermore an increase in DNA binding activity to a NFκB element occurred within a 342 base pair enhancer (I2E) of the SOD2 gene with 10 μM ATRA treatment. Reporter analysis showed that ATRA-mediated I2E dependent luciferase expression was attenuated upon mutation of the NFκB element, suggesting a contribution of this transcription factor in retinoid-mediated upregulation of MnSOD. This study identifies SOD2 to be a retinoid responsive gene and demonstrates activation of the NFκB pathway in response to ATRA treatment of SK-N-SH cells. These results suggest signaling events involving NFκB and SOD2 may contribute to the effects of retinoids used in cancer therapy.

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Section: Discussionmentioning

confidence: 58%

All-trans-retinoic acid induces manganese superoxide dismutase in human neuroblastoma through NF-κB

Kiningham

Cardozo

Cook

et al. 2008

Free Radical Biology and Medicine

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“…It is located in the promoter region of GRIN1 and could alter a consensus sequence for the p50 subunit of the transcription factor NF-kB. 19 The association analysis of G1001C polymorphism in the GRIN1 gene has been done by several groups, 19,21 -23 Association study in schizophrenia with microarray S Qin et al the allele frequency of the G366C polymorphism between patients and control individuals in the Japanese population. Also, their haplotype analysis showed a borderline significant result for the overall haplotype distribution.…”

Section: Discussionmentioning

confidence: 99%

“…9 -15 Mutation screening and association analysis for the NMDA receptors have been performed by several groups focusing mainly on the GRIN1 and GRIN2B genes. 16 -23 The association of the variants in GRIN1 and GRIN2B with schizophrenia has been established in several reports, 18,19 but not replicated in others. 16,22 Until now, GRIN1 and GRIN2B have always been studied individually.…”

Section: Introductionmentioning

confidence: 99%

An association study of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B) in schizophrenia with universal DNA microarray

Qin

Pan

et al. 2005

Eur J Hum Genet

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Dysfunction of the N-methyl-D-aspartate (NMDA) receptors has been implicated in the etiology of schizophrenia based on psychotomimetic properties of several antagonists and on observation of genetic animal models. To conduct association analysis of the NMDA receptors in the Chinese population, we examined 16 reported SNPs across the NMDA receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B), five of which were identified in the Chinese population. In this study, we combined universal DNA microarray and ligase detection reaction (LDR) for the purposes of association analysis, an approach we considered to be highly specific as well as offering a potentially high throughput of SNP genotyping. The association study was performed using 253 Chinese patients with schizophrenia and 140 Chinese control subjects. No significant frequency differences were found in the analysis of the alleles but some were found in the haplotypes of the GRIN2B gene. The interactions between the GRIN1 and GRIN2B genes were evaluated using the multifactor-dimensionality reduction (MDR) method, which showed a significant genetic interaction between the G1001C in the GRIN1 gene and the T4197C and T5988C polymorphisms in the GRIN2B gene. These findings suggest that the combined effects of the polymorphisms in the GRIN1 and GRIN2B genes might be involved in the etiology of schizophrenia.

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“…7 The GRIN1 gene has been found to be underexpressed in the cortex of schizophrenics 8 and has been suggested as a likely candidate in the pharmacogenetics of typical and atypical antipsychotics. 9 Evidence of studies on functional expression 10,11 and a mouse model 12 support the GRIN2B gene as a candidate for schizophrenia. Five polymorphisms including T-200G, 366C/G, 2664C/T, 4197T/C, and 5988T/C of GRIN2B have been the subject of schizophrenia association studies.…”

Section: Gene Variantsmentioning

confidence: 99%

Association study between the NMDA receptor 2B subunit gene (GRIN2B) and schizophrenia: A HuGE review and meta-analysis

2007

Genetics in Medicine

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Association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia

Cited by 58 publications

References 12 publications

All-trans-retinoic acid induces manganese superoxide dismutase in human neuroblastoma through NF-κB

All-trans-retinoic acid induces manganese superoxide dismutase in human neuroblastoma through NF-κB

An association study of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B) in schizophrenia with universal DNA microarray

Association study between the NMDA receptor 2B subunit gene (GRIN2B) and schizophrenia: A HuGE review and meta-analysis

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