Details

Autor(en) / Beteiligte

• LAMBERT, Jean-Charles
• GOUMIDI, Louisa
• ST CLAIR, David
• MANN, David M. A
• HARDY, John
• LENDON, Corinne L
• AMOUYEL, Philippe
• CHARTIER-HARLIN, Marie-Christine
• VRIEZE, Fabienne Wavrant-De
• FRIGARD, Bernard
• HARRIS, Judith M
• CUMMINGS, Alistair
• COATES, John
• PASQUIER, Florence
• COTTEL, Dominique
• GAILLAC, Marianne

Titel

The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease

Ist Teil von

• Human molecular genetics, 2000-09, Vol.9 (15), p.2275-2280

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2000

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Although the varepsilon4 allele of the apolipoprotein E gene appears as an important biological marker for Alzheimer's disease (AD) susceptibility, other genetic determinants are clearly implicated in the AD process. Here, we propose that a genetic variation in the transcriptional factor LBP-1c/CP2/LSF gene, located close to the LRP locus, is a genetic susceptibility factor for AD. We report an association between a non-coding polymorphism (G-->A) in the 3'-untranslated region of this gene and sporadic AD in French and British populations and a similar trend in a North American population. The combined analysis of these three independent populations provides evidence of a protective effect of the A allele (OR = 0.58, 95% CI 0.44-0.75). We describe a potential biologically relevant role for the A allele whereby it reduces binding to nuclear protein(s). The absence of the A allele was associated with a lower LBP-1c/CP2/LSF gene expression in lymphocytes from AD cases compared with controls. Our data suggest that polymorphic variation in the implication of the LBP-1c/CP2/LSF gene may be important for the pathogenesis of AD, particularly since LBP-1c/CP2/LSF interacts with proteins such as GSKbeta, Fe65 and certain factors involved in the inflammatory response.