Your browser doesn't support javascript.
loading
Potential involvement of GRIN2B encoding the NMDA receptor subunit NR2B in the spectrum of Alzheimer's disease.
Andreoli, Virginia; De Marco, Elvira Valeria; Trecroci, Francesca; Cittadella, Rita; Di Palma, Gemma; Gambardella, Antonio.
Afiliação
  • Andreoli V; Institute of Neurological Sciences, National Research Council, Pianolago di Mangone, Cosenza, Italy, v.andreoli@isn.cnr.it.
J Neural Transm (Vienna) ; 121(5): 533-42, 2014 May.
Article em En | MEDLINE | ID: mdl-24292895
ABSTRACT
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 ε4 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de N-Metil-D-Aspartato / Polimorfismo de Nucleotídeo Único / Doença de Alzheimer / Mutação Tipo de estudo: Prognostic_studies Limite: Aged / Female / Humans / Male País/Região como assunto: Europa Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de N-Metil-D-Aspartato / Polimorfismo de Nucleotídeo Único / Doença de Alzheimer / Mutação Tipo de estudo: Prognostic_studies Limite: Aged / Female / Humans / Male País/Região como assunto: Europa Idioma: En Ano de publicação: 2014 Tipo de documento: Article