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-DeVrièze; M. Ezquerra-Trabalon; P. Amouyel; J. Hardy; M. Haltia; F. Valdivieso; A. M. Goate; J. Pérez-Tur; C. L. Lendon; Marie Christine Chartier-Harlin

doi:10.1212/WNL.59.1.59

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-DeVrièze, M. Ezquerra-Trabalon, P. Amouyel, J. Hardy, M. Haltia, F. Valdivieso, A. M. Goate, J. Pérez-Tur, C. L. Lendon, Marie Christine Chartier-Harlin

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

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Abstract

Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-ε4 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-ε4 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-ε4 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 (US)
Pages (from-to)	59-66
Number of pages	8
Journal	Neurology
Volume	59
Issue number	1
DOIs	https://doi.org/10.1212/WNL.59.1.59
State	Published - Jul 9 2002

ASJC Scopus subject areas

Clinical Neurology

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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(1), 59-66. https://doi.org/10.1212/WNL.59.1.59

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-DeVrièze, F, Ezquerra-Trabalon, M, Amouyel, P, Hardy, J, Haltia, M, Valdivieso, F, Goate, AM, Pérez-Tur, J, Lendon, CL & Chartier-Harlin, MC 2002, 'Contribution of APOE promoter polymorphisms to Alzheimer's disease risk', Neurology, vol. 59, no. 1, pp. 59-66. https://doi.org/10.1212/WNL.59.1.59

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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-ε4 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-ε4 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-ε4 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.",

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-DeVri{\`e}ze and M. Ezquerra-Trabalon and P. Amouyel and J. Hardy and M. Haltia and F. Valdivieso and Goate, {A. M.} and J. P{\'e}rez-Tur and Lendon, {C. L.} and Chartier-Harlin, {Marie Christine}",

year = "2002",

month = jul,

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doi = "10.1212/WNL.59.1.59",

language = "English (US)",

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pages = "59--66",

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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-DeVrièze, F.

AU - Ezquerra-Trabalon, M.

AU - Amouyel, P.

AU - Hardy, J.

AU - Haltia, M.

AU - Valdivieso, F.

AU - Goate, A. M.

AU - Pérez-Tur, J.

AU - Lendon, C. L.

AU - Chartier-Harlin, Marie Christine

PY - 2002/7/9

Y1 - 2002/7/9

N2 - Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-ε4 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-ε4 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-ε4 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-ε4 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-ε4 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-ε4 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.

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JO - Neurology

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Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

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