Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

Neurology. 2002 Jul 9;59(1):59-66. doi: 10.1212/wnl.59.1.59.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic / genetics*
  • Risk Factors

Substances

  • Apolipoprotein E4
  • Apolipoproteins E