Lack of independent associations of apolipoprotein E promoter and intron 1 polymorphisms with Alzheimer's disease

Neurosci Lett. 1999 Sep 17;272(3):155-8. doi: 10.1016/s0304-3940(99)00602-3.


Several studies have demonstrated genetic associations between Alzheimer's disease (AD) and polymorphisms in the promoter/enhancer regions of the apolipoprotein E (APOE) gene. These studies raise the possibility that APOE transcription control may be involved in altered risks for AD. We evaluated polymorphic sites in the intron-1 enhancer element (IE-1G/C) and in the APOE promoter (-219G/T). For the IE-1 polymorphism, we analyzed 433 individuals (183 AD and 250 controls), and found a strong linkage between the IE-1G allele and APOE-epsilon4. When we controlled for this linkage using log-linear model analysis, we found no independent association between the IE-1 polymorphism and AD. For the -219 polymorphism, we analyzed 475 individuals (168 AD cases, 234 controls, and 73 cases of cerebral amyloid angiopathy (CAA)). We found strong linkages between the -219G allele and APOE-epsilon2 and between the -219 T allele and APOE-epsilon4. Controlling for these linkages, we found no independent association between the -219 polymorphism and AD or CAA. Thus, our studies do not support independent associations between AD and either the IE-1 or the -219 polymorphisms.

Publication types

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

MeSH terms

  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoprotein E2
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Cerebral Amyloid Angiopathy / genetics
  • DNA / analysis
  • DNA / genetics
  • DNA Primers
  • Genetic Linkage / genetics
  • Humans
  • Introns / genetics*
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors


  • Apolipoprotein E2
  • Apolipoprotein E4
  • Apolipoproteins E
  • DNA Primers
  • DNA