Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

JC Lambert; L Goumidi; L Myllykangas; F Wavrant-De Vrieze; J Wang; MJ Bullido; JM Harris; MJ Artiga; D Hernandez; JM Kwon; B Frigard; R Peterson; A Cumming; F Pasquier; T Polvikoski; I Sastre; P Tienari; A Frank; R Sulkava; JC Morris; D St. Clair; DM Mann; P Amouyel; J Hardy; F Valdivieso; AM Goate; M Haltia; J Perez-Tur; Corinne Lendon; M-C Chartier-Harlin

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

JC Lambert, L Goumidi, L Myllykangas, F Wavrant-De Vrieze, J Wang, MJ Bullido, JM Harris, MJ Artiga, D Hernandez, JM Kwon, B Frigard, R Peterson, A Cumming, F Pasquier, T Polvikoski, I Sastre, P Tienari, A Frank, R Sulkava, JC MorrisD St. Clair, DM Mann, P Amouyel, J Hardy, F Valdivieso, AM Goate, M Haltia, J Perez-Tur, Corinne Lendon, M-C Chartier-Harlin

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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	9
Issue number	59(1)
Publication status	Published - 31 Dec 2002

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Lambert, JC., Goumidi, L., Myllykangas, L., Wavrant-De Vrieze, F., Wang, J., Bullido, MJ., Harris, JM., Artiga, MJ., Hernandez, D., Kwon, JM., Frigard, B., Peterson, R., Cumming, A., Pasquier, F., Polvikoski, T., Sastre, I., Tienari, P., Frank, A., Sulkava, R., ... Chartier-Harlin, M-C. (2002). Contribution of APOE promoter polymorphisms to Alzheimer's disease risk. Neurology, 9(59(1)), 59-66.

@article{c13261fb53ec49a4b90e752117da9fbf,

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.",

author = "JC Lambert and L Goumidi and L Myllykangas and {Wavrant-De Vrieze}, F and J Wang and MJ Bullido and JM Harris and MJ Artiga and D Hernandez and JM Kwon and B Frigard and R Peterson and A Cumming and F Pasquier and T Polvikoski and I Sastre and P Tienari and A Frank and R Sulkava and JC Morris and {St. Clair}, D and DM Mann and P Amouyel and J Hardy and F Valdivieso and AM Goate and M Haltia and J Perez-Tur and Corinne Lendon and M-C Chartier-Harlin",

year = "2002",

month = dec,

day = "31",

language = "English",

volume = "9",

pages = "59--66",

journal = "Neurology",

publisher = "American Academy of Neurology",

number = "59(1)",

}

Lambert, JC, Goumidi, L, Myllykangas, L, Wavrant-De Vrieze, F, Wang, J, Bullido, MJ, Harris, JM, Artiga, MJ, Hernandez, D, Kwon, JM, Frigard, B, Peterson, R, Cumming, A, Pasquier, F, Polvikoski, T, Sastre, I, Tienari, P, Frank, A, Sulkava, R, Morris, JC, St. Clair, D, Mann, DM, Amouyel, P, Hardy, J, Valdivieso, F, Goate, AM, Haltia, M, Perez-Tur, J, Lendon, C & Chartier-Harlin, M-C 2002, 'Contribution of APOE promoter polymorphisms to Alzheimer's disease risk', Neurology, vol. 9, no. 59(1), pp. 59-66.

TY - JOUR

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

AU - Lambert, JC

AU - Goumidi, L

AU - Myllykangas, L

AU - Wavrant-De Vrieze, F

AU - Wang, J

AU - Bullido, MJ

AU - Harris, JM

AU - Artiga, MJ

AU - Hernandez, D

AU - Kwon, JM

AU - Frigard, B

AU - Peterson, R

AU - Cumming, A

AU - Pasquier, F

AU - Polvikoski, T

AU - Sastre, I

AU - Tienari, P

AU - Frank, A

AU - Sulkava, R

AU - Morris, JC

AU - St. Clair, D

AU - Mann, DM

AU - Amouyel, P

AU - Hardy, J

AU - Valdivieso, F

AU - Goate, AM

AU - Haltia, M

AU - Perez-Tur, J

AU - Lendon, Corinne

AU - Chartier-Harlin, M-C

PY - 2002/12/31

Y1 - 2002/12/31

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.

M3 - Article

C2 - 12105308

VL - 9

SP - 59

EP - 66

JO - Neurology

JF - Neurology

IS - 59(1)

ER -

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

Abstract

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