Linked Life Data

12724619

Source:http://linkedlifedata.com/resource/pubmed/id/12724619

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-5-1
pubmed:abstractText
Hypofunction of the N-methyl-D-aspartate (NMDA) receptor has been hypothesized to underlie the pathophysiology of schizophrenia, based on the observation that non-competitive antagonists of the NMDA receptor, such as phencyclidine, induce schizophrenia-like symptoms. Mice lacking the NR2A subunit of the NMDA receptor complex are known to display abnormal behaviour, similar to schizophrenic symptoms. The expression of NR2A starts at puberty, a period corresponding to the clinical onset of schizophrenia. This evidence suggests that the NR2A (GRIN2A) gene may play a role in the development of schizophrenia and disease phenotypes. In this study, we performed a genetic analysis of this gene in schizophrenia. Analysis of the GRIN2A gene detected four single nucleotide polymorphisms, and a variable (GT)(n) repeat in the promoter region of the gene. A case-control study (375 schizophrenics and 378 controls) demonstrated evidence of an association between the repeat polymorphism and the disease (P = 0.05, Mann-Whitney test), with longer alleles overly represented in patients. An in-vitro promoter assay revealed a length dependent inhibition of transcriptional activity by the (GT)(n) repeat, which was consistent with a receptor binding assay in postmortem brains. Significantly, the score of symptom severity in chronic patients correlated with repeat size (P = 0.01, Spearman's Rank test). These results illustrate a genotype-phenotype correlation in schizophrenia and suggest that the longer (GT)(n) stretch may act as a risk-conferring factor that worsens chronic outcome by reducing GRIN2A levels in the brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12724619-Adult, pubmed-meshheading:12724619-Aged, pubmed-meshheading:12724619-Base Sequence, pubmed-meshheading:12724619-DNA, Complementary, pubmed-meshheading:12724619-DNA Primers, pubmed-meshheading:12724619-Female, pubmed-meshheading:12724619-Gene Expression Regulation, pubmed-meshheading:12724619-Humans, pubmed-meshheading:12724619-Male, pubmed-meshheading:12724619-Microsatellite Repeats, pubmed-meshheading:12724619-Middle Aged, pubmed-meshheading:12724619-Polymorphism, Genetic, pubmed-meshheading:12724619-Polymorphism, Single Nucleotide, pubmed-meshheading:12724619-Prognosis, pubmed-meshheading:12724619-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:12724619-Reference Values, pubmed-meshheading:12724619-Schizophrenia, pubmed-meshheading:12724619-Transcription, Genetic, pubmed-meshheading:12724619-Treatment Outcome
pubmed:year
2003
pubmed:articleTitle
A microsatellite repeat in the promoter of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia.
pubmed:affiliation
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
pubmed:publicationType
Journal Article, Comparative Study