Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

J C  Lambert; L  Araria-Goumidi; L  Myllykangas; C  Ellis; J C  Wang; M J  Bullido; J M  Harris; M J  Artiga; D  Hernandez; J M  Kwon; B  Frigard; R C  Petersen; A M  Cumming; F  Pasquier; I  Sastre; P J  Tienari; A  Frank; R  Sulkava; J C  Morris; D  St Clair; D M  Mann; F  Wavrant-DeVrieze; M  Ezquerra-Trabalon; P  Amouyel; J  Hardy; M  Haltia; F  Valdivieso; A M  Goate; J  Perez-Tur; C L  Lendon; M C  Chartier-Harlin

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

J C Lambert, L Araria-Goumidi, L Myllykangas, C Ellis, J C Wang, M J Bullido, J M Harris, M J Artiga, D Hernandez, J M Kwon, B Frigard, R C Petersen, A M Cumming, F Pasquier, I Sastre, P J Tienari, A Frank, R Sulkava, J C Morris, D St ClairD M Mann, F Wavrant-DeVrieze, M Ezquerra-Trabalon, P Amouyel, J Hardy, M Haltia, F Valdivieso, A M Goate, J Perez-Tur, C L Lendon, M C Chartier-Harlin

Applied Medicine

Research output: Contribution to journal › Article

104 Citations (Scopus)

Abstract

Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. Background: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. Methods: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. Results: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. Conclusion: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.

Original language	English
Pages (from-to)	59-66
Number of pages	8
Journal	Neurology
Volume	59
Publication status	Published - 2002

Keywords

HUMAN APOLIPOPROTEIN-E
AMYLOID-BETA-PEPTIDE
REGULATORY REGION
E GENOTYPE
E GENE
INDEPENDENT RISK
MOUSE MODEL
ONSET
ASSOCIATION
POPULATION

Cite this

Lambert, J. C., Araria-Goumidi, L., Myllykangas, L., Ellis, C., Wang, J. C., Bullido, M. J., Harris, J. M., Artiga, M. J., Hernandez, D., Kwon, J. M., Frigard, B., Petersen, R. C., Cumming, A. M., Pasquier, F., Sastre, I., Tienari, P. J., Frank, A., Sulkava, R., Morris, J. C., ... Chartier-Harlin, M. C. (2002). Contribution of APOE promoter polymorphisms to Alzheimer's disease risk. Neurology, 59, 59-66.

Lambert, JC, Araria-Goumidi, L, Myllykangas, L, Ellis, C, Wang, JC, Bullido, MJ, Harris, JM, Artiga, MJ, Hernandez, D, Kwon, JM, Frigard, B, Petersen, RC, Cumming, AM, Pasquier, F, Sastre, I, Tienari, PJ, Frank, A, Sulkava, R, Morris, JC, St Clair, D, Mann, DM, Wavrant-DeVrieze, F, Ezquerra-Trabalon, M, Amouyel, P, Hardy, J, Haltia, M, Valdivieso, F, Goate, AM, Perez-Tur, J, Lendon, CL & Chartier-Harlin, MC 2002, 'Contribution of APOE promoter polymorphisms to Alzheimer's disease risk', Neurology, vol. 59, pp. 59-66.

@article{9534b1ad2a95476cbc1ced282ba90a8c,

title = "Contribution of APOE promoter polymorphisms to Alzheimer's disease risk",

abstract = "Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. Background: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. Methods: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. Results: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. Conclusion: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.",

keywords = "HUMAN APOLIPOPROTEIN-E, AMYLOID-BETA-PEPTIDE, REGULATORY REGION, E GENOTYPE, E GENE, INDEPENDENT RISK, MOUSE MODEL, ONSET, ASSOCIATION, POPULATION",

author = "Lambert, {J C} and L Araria-Goumidi and L Myllykangas and C Ellis and Wang, {J C} and Bullido, {M J} and Harris, {J M} and Artiga, {M J} and D Hernandez and Kwon, {J M} and B Frigard and Petersen, {R C} and Cumming, {A M} and F Pasquier and I Sastre and Tienari, {P J} and A Frank and R Sulkava and Morris, {J C} and {St Clair}, D and Mann, {D M} and F Wavrant-DeVrieze and M Ezquerra-Trabalon and P Amouyel and J Hardy and M Haltia and F Valdivieso and Goate, {A M} and J Perez-Tur and Lendon, {C L} and Chartier-Harlin, {M C}",

year = "2002",

language = "English",

volume = "59",

pages = "59--66",

journal = "Neurology",

issn = "0028-3878",

publisher = "AAN Enterprises",

}

TY - JOUR

T1 - Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

AU - Lambert, J C

AU - Araria-Goumidi, L

AU - Myllykangas, L

AU - Ellis, C

AU - Wang, J C

AU - Bullido, M J

AU - Harris, J M

AU - Artiga, M J

AU - Hernandez, D

AU - Kwon, J M

AU - Frigard, B

AU - Petersen, R C

AU - Cumming, A M

AU - Pasquier, F

AU - Sastre, I

AU - Tienari, P J

AU - Frank, A

AU - Sulkava, R

AU - Morris, J C

AU - St Clair, D

AU - Mann, D M

AU - Wavrant-DeVrieze, F

AU - Ezquerra-Trabalon, M

AU - Amouyel, P

AU - Hardy, J

AU - Haltia, M

AU - Valdivieso, F

AU - Goate, A M

AU - Perez-Tur, J

AU - Lendon, C L

AU - Chartier-Harlin, M C

PY - 2002

Y1 - 2002

N2 - Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. Background: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. Methods: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. Results: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. Conclusion: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.

AB - Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. Background: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. Methods: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. Results: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. Conclusion: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.

KW - HUMAN APOLIPOPROTEIN-E

KW - AMYLOID-BETA-PEPTIDE

KW - REGULATORY REGION

KW - E GENOTYPE

KW - E GENE

KW - INDEPENDENT RISK

KW - MOUSE MODEL

KW - ONSET

KW - ASSOCIATION

KW - POPULATION

M3 - Article

SN - 0028-3878

VL - 59

SP - 59

EP - 66

JO - Neurology

JF - Neurology

ER -

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

Abstract

Keywords

Fingerprint

Cite this