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

J C Lambert, L Goumidi, F Wavrant-De Vrieze, B Frigard, J M Harris, A Cummings, J Coates, F Pasquier, D Cottel, M Gaillac, D St Clair, D M A Mann, J Hardy, C L Lendon, P Amouyel, M C Chartier-Harlin

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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 languageEnglish
Pages (from-to)2275-2280
Number of pages6
JournalHuman Molecular Genetics
Volume9
Publication statusPublished - 2000

Keywords

  • SIMPLEX VIRUS TYPE-1
  • APOLIPOPROTEIN-E
  • MOLECULAR-CLONING
  • GENOMIC STRUCTURE
  • FACTOR CP2
  • LRP GENE
  • ASSOCIATION
  • ALPHA-2-MACROGLOBULIN
  • DEMENTIA
  • LOCUS

Cite this

Lambert, J. C., Goumidi, L., Wavrant-De Vrieze, F., Frigard, B., Harris, J. M., Cummings, A., Coates, J., Pasquier, F., Cottel, D., Gaillac, M., St Clair, D., Mann, D. M. A., Hardy, J., Lendon, C. L., Amouyel, P., & Chartier-Harlin, M. C. (2000). The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease. Human Molecular Genetics, 9, 2275-2280.