Comprehensive association analysis of APOE regulatory region polymorphisms in Alzheimer disease.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nicodemus, KK; Stenger, JE; Schmechel, DE; Welsh-Bohmer, KA; Saunders, AM; Roses, AD; Gilbert, JR; Vance, JM; Haines, JL; Pericak-Vance, MA; Martin, ER

Published Date

  • December 2004

Published In

Volume / Issue

  • 5 / 4

Start / End Page

  • 201 - 208

PubMed ID

  • 15455263

Pubmed Central ID

  • 15455263

International Standard Serial Number (ISSN)

  • 1364-6745

Digital Object Identifier (DOI)

  • 10.1007/s10048-004-0189-9


  • eng

Conference Location

  • United States