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

Research output: Contribution to journalArticle

89 Citations (Scopus)


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 languageEnglish
Pages (from-to)59-66
Number of pages8
Publication statusPublished - 2002


  • E GENE

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.