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 W Vrièze; B Frigard; Judith Harris; A Cummings; J Coates; F Pasquier; D Cottel; M Gaillac; D St Clair; D M Mann; J Hardy; C L Lendon; P Amouyel; M C Chartier-Harlin

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 W Vrièze, B Frigard, Judith Harris, A Cummings, J Coates, F Pasquier, D Cottel, M Gaillac, D St Clair, D M Mann, J Hardy, C L Lendon, P Amouyel, M C Chartier-Harlin

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2275-80
Number of pages	6
Journal	Human Molecular Genetics
Volume	9
Issue number	15
Publication status	Published - 2000

Cite this

Lambert, J. C., Goumidi, L., Vrièze, F. W., Frigard, B., Harris, J., Cummings, A., Coates, J., Pasquier, F., Cottel, D., Gaillac, M., St Clair, D., Mann, D. M., 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(15), 2275-80.

@article{53be8c3df22f4a7ca034bbf145256391,

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

abstract = "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.",

author = "Lambert, {J C} and L Goumidi and Vri{\`e}ze, {F W} and B Frigard and Judith Harris and A Cummings and J Coates and F Pasquier and D Cottel and M Gaillac and {St Clair}, D and Mann, {D M} and J Hardy and Lendon, {C L} and P Amouyel and Chartier-Harlin, {M C}",

year = "2000",

language = "English",

volume = "9",

pages = "2275--80",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "15",

}

Lambert, JC, Goumidi, L, Vrièze, FW, Frigard, B, Harris, J, Cummings, A, Coates, J, Pasquier, F, Cottel, D, Gaillac, M, St Clair, D, Mann, DM, 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, no. 15, pp. 2275-80.

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 - Vrièze, F W

AU - Frigard, B

AU - Harris, Judith

AU - Cummings, A

AU - Coates, J

AU - Pasquier, F

AU - Cottel, D

AU - Gaillac, M

AU - St Clair, D

AU - Mann, D M

AU - Hardy, J

AU - Lendon, C L

AU - Amouyel, P

AU - Chartier-Harlin, M C

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

M3 - Article

C2 - 11001930

SN - 0964-6906

VL - 9

SP - 2275

EP - 2280

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 15

ER -

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

Abstract

Fingerprint

Cite this