Association of APOE 2/3/4 and promoter gene variants with dementia but not cardiovascular mortality in old age
article
The common apolipoprotein E (APOE) alleles ε2, ε3, and ε4 are associated with the risk of dementia and cardiovascular disease. Recently, two functional variants (-219G/T and -491A/T) were identified in the promoter of the APOE gene that enable a further characterization of the role of the APOE locus in disease. We investigated the contribution of these APOE gene variants to dementia and cardiovascular mortality in old age using a population-based cohort of 648 subjects aged 85 years and over (Leiden 85-Plus Study). Genotypes containing an APOE ε4 allele were associated with a 4.1-fold (95% CI, 2.2-7.7) increased risk of dementia as compared to the ε3/ε3 genotype in old subjects. Moreover, homozygosity for the -219T allele was found to be associated with a 2.4-fold (95% CI, 1.0-5.8) increased risk independently of ε2 and ε4; the -491A/T variant was not associated with dementia. Over a 10-year follow-up period, the risk of cardiovascular mortality was not increased among ε4 carriers (RR, 0.6; 95% CI, 0.4-1.0) or -219T homozygous subjects (RR, 1.1; 95% CI, 0.7-1.7), nor did it decrease among -491T homozygous subjects (RR, 1.4; 95% CI, 0.6-3.1). In conclusion, both the APOE ε2/ε3/ε4 and the -219G/T variant were identified as risk factors for dementia but not cardiovascular mortality in old age. Our results support the hypothesis that both the isoform and the amount of APOE may influence the risk of dementia. Furthermore, they emphasize that variation at the APOE locus has a higher impact on the risk of dementia than on the risk of cardiovascular disease in old age. © 2001 Wiley-Liss, Inc. Chemicals / CAS DNA, 9007-49-2; Apolipoprotein E2; Apolipoprotein E3; Apolipoprotein E4; Apolipoproteins E; DNA, 9007-49-2
Topics
Apolipoprotein ECardiovascular diseaseDementiaLongevity geneticsPromoter polymorphismapolipoprotein Eapolipoprotein Eapolipoprotein E2apolipoprotein E3apolipoprotein E4DNAadultagedallelearticlecardiovascular diseasecardiovascular riskcohort analysisdementiafemalefollow upgene locusgenetic riskgenetic variabilitygenotypehomozygosityhumanmajor clinical studymalemortalitypopulation researchpriority journalpromoter regionrisk assessmentagecardiovascular diseasedementiagene frequencygeneticspromoter regionrisk factorsurvival rateAge FactorsAgedAged, 80 and overApolipoprotein E2Apolipoprotein E3Apolipoprotein E4Apolipoproteins ECardiovascular DiseasesCohort StudiesDementiaDNAFemaleGene FrequencyGenotypeHumansMalePromoter Regions (Genetics)Risk FactorsSurvival RateVariation (Genetics)
TNO Identifier
953609
ISSN
01487299
Source
American Journal of Medical Genetics, 107(3), pp. 201-208.
Pages
201-208
Files
To receive the publication files, please send an e-mail request to TNO Repository.