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

    Research output: Contribution to journalArticle

    92 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
    Issue number59(1)
    Publication statusPublished - 31 Dec 2002


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