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

TitleComprehensive association analysis of APOE regulatory region polymorphisms in Alzheimer disease.
Publication TypeJournal Article
Year of Publication2004
AuthorsNicodemus, KK, Stenger, JE, Schmechel, DE, Welsh-Bohmer, KA, Saunders, AM, Roses, AD, Gilbert, JR, Vance, JM, Haines, JL, Pericak-Vance, MA, Martin, ER
Date Published2004 Dec
KeywordsAge of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Case-Control Studies, Family Health, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Linkage Disequilibrium, Male, Polymorphism, Genetic, Risk Factors

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.

Alternate JournalNeurogenetics
PubMed ID15455263
Grant ListU24 AG021886 / AG / NIA NIH HHS / United States
R01 NS31153 / NS / NINDS NIH HHS / United States
R01 AG 19757 / AG / NIA NIH HHS / United States
R01 AG021547 / AG / NIA NIH HHS / United States
R01 AG20135 / AG / NIA NIH HHS / United States