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

Research output: Contribution to journalArticle

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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., ... 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.

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

In: Human Molecular Genetics, Vol. 9, 2000, p. 2275-2280.

Research output: Contribution to journalArticle

Lambert, JC, Goumidi, L, Wavrant-De Vrieze, F, Frigard, B, Harris, JM, Cummings, A, Coates, J, Pasquier, F, Cottel, D, Gaillac, M, St Clair, D, Mann, DMA, Hardy, J, Lendon, CL, Amouyel, P & Chartier-Harlin, MC 2000, 'The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease', Human Molecular Genetics, vol. 9, pp. 2275-2280.
Lambert JC, Goumidi L, Wavrant-De Vrieze F, Frigard B, Harris JM, Cummings A et al. The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease. Human Molecular Genetics. 2000;9:2275-2280.
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 . / The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease. In: Human Molecular Genetics. 2000 ; Vol. 9. pp. 2275-2280.
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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.",
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TY - JOUR

T1 - The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease

AU - Lambert, J C

AU - Goumidi, L

AU - Wavrant-De Vrieze, F

AU - Frigard, B

AU - Harris, J M

AU - Cummings, A

AU - Coates, J

AU - Pasquier, F

AU - Cottel, D

AU - Gaillac, M

AU - St Clair, D

AU - Mann, D M A

AU - Hardy, J

AU - Lendon, C L

AU - Amouyel, P

AU - Chartier-Harlin, M C

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - SIMPLEX VIRUS TYPE-1

KW - APOLIPOPROTEIN-E

KW - MOLECULAR-CLONING

KW - GENOMIC STRUCTURE

KW - FACTOR CP2

KW - LRP GENE

KW - ASSOCIATION

KW - ALPHA-2-MACROGLOBULIN

KW - DEMENTIA

KW - LOCUS

M3 - Article

VL - 9

SP - 2275

EP - 2280

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

ER -