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Human Molecular Genetics, 2000, Vol. 9, No. 15 2275-2280
© 2000 Oxford University Press

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

Jean-Charles Lambert1,2, Louisa Goumidi1, Fabienne Wavrant-De Vrièze3, Bernard Frigard4, Judith M. Harris2, Alistair Cummings5, John Coates2, Florence Pasquier6, Dominique Cottel1, Marianne Gaillac1, David St Clair5, David M.A. Mann7, John Hardy3, Corinne L. Lendon2, Philippe Amouyel1 and Marie-Christine Chartier-Harlin1,+

1INSERM U508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille Cédex, France, 2Molecular Psychiatry Department, Division of Neuroscience, Queen Elisabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, 3Birdsall Building, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA, 4Centre de Gériatrie de Wasquehal-Moulinel, rue Salvador Allende, BP 165, 59444 Wasquehal, France, 5Department of Mental Health, University of Aberdeen, Aberdeen,UK, 6CHRU de Lille, Clinique Neurologique, Centre de la Mémoire, Hôpital Salengro, 59037 Lille Cédex, France and 7Laboratory Medicine Academic Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK

Although the {varepsilon}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 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 GSKß, Fe65 and certain factors involved in the inflammatory response.

+ To whom correspondence should be addresssed. Tel: +33 3 20 87 72 28; Fax: +33 3 20 87 78 94; Email: marie-christine.chartier@pasteur-lille.fr


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