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Potential involvement of GRIN2B encoding the NMDA receptor subunit NR2B in the spectrum of Alzheimer's disease.

Authors: Andreoli, Virginia  De Marco, Elvira Valeria  Trecroci, Francesca  Cittadella, Rita  Di Palma, Gemma  Gambardella, Antonio 
Citation: Andreoli V, etal., J Neural Transm (Vienna). 2014 May;121(5):533-42. doi: 10.1007/s00702-013-1125-7. Epub 2013 Dec 1.
Pubmed: (View Article at PubMed) PMID:24292895
DOI: Full-text: DOI:10.1007/s00702-013-1125-7

Increasing evidence links dysregulation of NR2B-containing N-methyl-D-aspartate receptor remodelling and trafficking to Alzheimer's disease (AD). This theme offers the possibility that the GRIN2B gene, encoding this selective NR2B subunit, represents a potential molecular modulating factor for this disease. Based on this hypothesis, we carried out a mutation scanning of exons and flanking regions of GRIN2B in a well-characterized cohort of AD patients, recruited from Southern Italy. A "de novo" p.K1293R mutation, affecting a highly conserved residue of the protein in the C-terminal domain, was observed for the first time in a woman with familial AD, as the only genetic alteration of relevance. Moreover, an association study between the other detected sequence variants and AD was performed. In particular, the study was focused on five identified single nucleotide polymorphisms: rs7301328, rs1805482, rs3026160, rs1806191 and rs1806201, highlighting a significant contribution from the GRIN2B rs1806201 T allele towards disease susceptibility [adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI) 1.40-2.63, p < 0.001, after correction for sex, age, and APOE e4 genotype]. This was confirmed by haplotype analysis that identified a specific haplotype, carrying the rs1806201 T allele (CCCTC), over-represented in patients versus controls (adjusted OR = 6.03; p < 0.0001). Although the pathogenic role of the GRIN2B-K1293R mutation in AD is not clear, our data advocate that genetic variability in the GRIN2B gene, involved in synaptic functioning, might provide valuable insights into disease pathogenesis, continuing to attract significant attention in biomedical research on its genetic and functional role.

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CRRD Object Information
CRRD ID: 13792709
Created: 2018-09-21
Species: All species
Last Modified: 2018-09-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.