Comprehensive association analysis of APOE regulatory region polymorphisms in Alzheimer disease

Kristin K. Nicodemus, Judith E. Stenger, Donald E. Schmechel, Kathleen A. Welsh-Bohmer, Ann M. Saunders, Allen D. Roses, John R. Gilbert, Jeffery M. Vance, Jonathan L. Haines, Margaret A. Pericak-Vance, Eden R. Martin

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Several recent case-control studies have examined the association between single nucleotide polymorphisms (SNPs) in the promoter region of the apolipoprotein E gene (APOE) and risk of Alzheimer disease (AD), with conflicting results. We assessed the relation between five APOE region SNPs and risk of AD in both case-control and family-based analyses. We observed a statistically significant association with the +5361T allele in the overall case-control analysis (P value=0.04) after adjusting for the known effect of the APOE-4 allele. Further analysis revealed this association to be limited to carriers of the APOE-4 allele. Age-stratified analyses in the patients with age at onset of 80 years or greater and age-matched controls showed that the -219T allele (P value=0.009) and the +113C allele (P value=0.03) are associated with increased risk of AD. Despite these findings, haplotype and family-based association analyses were unable to provide evidence that the APOE region SNPs influenced risk of AD independent of the APOE-4 allele. In addition to risk, we tested for association between the SNPs and age at onset of AD, but found no association in the case-control or family based analyses. In conclusion, SNPs +5361, or a SNP in strong linkage disequilibrium, may confer some additional risk for developing AD beyond the risk due to APOE-4; however, the effect independent of APOE-4 is likely to be small.

Original languageEnglish (US)
Pages (from-to)201-208
Number of pages8
Issue number4
StatePublished - Dec 2004
Externally publishedYes


  • Age at onset
  • Alzheimer disease
  • APOE
  • Haplotype
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)


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