A new polymorphism in the APOE promoter associated with risk of developing Alzheimer's disease

Hum Mol Genet. 1998 Mar;7(3):533-40. doi: 10.1093/hmg/7.3.533.


The epsilon4 allele of the Apolipoprotein E gene (APOE), one of the main allele of APOE polymorphism, is a major risk factor for the development of Alzheimer's disease. However, several data suggest that genetic factors, within the APOE locus, may also modulate the risk associated with this polymorphism. We look for new mutations in the APOE promoter, susceptible to modify the risk associated with the APOE epsilon4 allele. We characterised a G-->T mutation at -186 bp of the APOE gene TATA box, named Th1/E47cs. This new polymorphism is located in a consensus sequence of a potential transcriptional (Th1/E47) factor binding site. We studied the impact of this new polymorphism with those of other markers of the APOE locus in a large case-control study and observed that Th1/E47cs modulated the influence of the APOE epsilon4 allele on the risk of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Base Sequence
  • Binding Sites
  • Consensus Sequence
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Point Mutation
  • Polymorphism, Genetic*
  • Reference Values
  • Risk Factors
  • TATA Box*
  • Transcription Factors / metabolism


  • Apolipoprotein E4
  • Apolipoproteins E
  • Transcription Factors