The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease.
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.
Lambert
J C
JC
INSERM U508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille Cédex, France.
Goumidi
L
L
Vrièze
F W
FW
Frigard
B
B
Harris
J M
JM
Cummings
A
A
Coates
J
J
Pasquier
F
F
Cottel
D
D
Gaillac
M
M
St Clair
D
D
Mann
D M
DM
Hardy
J
J
Lendon
C L
CL
Amouyel
P
P
Chartier-Harlin
M C
MC
D020413:3' Untranslated Regions; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C501906:TFCP2 protein, human; D014157:Transcription Factors