Abstract
Although the epsilon 4 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 elf 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 GSK beta, Fe65 and certain factors involved in the inflammatory response.
Original language | English |
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Pages (from-to) | 2275-2280 |
Number of pages | 6 |
Journal | Human Molecular Genetics |
Volume | 9 |
Publication status | Published - 2000 |
Keywords
- SIMPLEX VIRUS TYPE-1
- APOLIPOPROTEIN-E
- MOLECULAR-CLONING
- GENOMIC STRUCTURE
- FACTOR CP2
- LRP GENE
- ASSOCIATION
- ALPHA-2-MACROGLOBULIN
- DEMENTIA
- LOCUS