Tags

Type your tag names separated by a space and hit enter

Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age.
Am J Med Genet 2002; 107(3):201-8AJ

Abstract

The common apolipoprotein E (APOE) alleles epsilon2, epsilon3, and epsilon4 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 epsilon4 allele were associated with a 4.1-fold (95% CI, 2.2-7.7) increased risk of dementia as compared to the epsilon3/epsilon3 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 epsilon2 and epsilon4; 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 epsilon4 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 epsilon2/epsilon3/epsilon4 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.

Authors+Show Affiliations

Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands. B.T.Heijmans@lumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11807900

Citation

Heijmans, Bastiaan T., et al. "Association of APOE Epsilon2/epsilon3/epsilon4 and Promoter Gene Variants With Dementia but Not Cardiovascular Mortality in Old Age." American Journal of Medical Genetics, vol. 107, no. 3, 2002, pp. 201-8.
Heijmans BT, Slagboom PE, Gussekloo J, et al. Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age. Am J Med Genet. 2002;107(3):201-8.
Heijmans, B. T., Slagboom, P. E., Gussekloo, J., Droog, S., Lagaay, A. M., Kluft, C., ... Westendorp, R. G. (2002). Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age. American Journal of Medical Genetics, 107(3), pp. 201-8.
Heijmans BT, et al. Association of APOE Epsilon2/epsilon3/epsilon4 and Promoter Gene Variants With Dementia but Not Cardiovascular Mortality in Old Age. Am J Med Genet. 2002 Jan 22;107(3):201-8. PubMed PMID: 11807900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age. AU - Heijmans,Bastiaan T, AU - Slagboom,P Eline, AU - Gussekloo,Jacobijn, AU - Droog,Simone, AU - Lagaay,A Margot, AU - Kluft,Cornelis, AU - Knook,Dick L, AU - Westendorp,Rudi G J, PY - 2002/1/25/pubmed PY - 2002/2/13/medline PY - 2002/1/25/entrez SP - 201 EP - 8 JF - American journal of medical genetics JO - Am. J. Med. Genet. VL - 107 IS - 3 N2 - The common apolipoprotein E (APOE) alleles epsilon2, epsilon3, and epsilon4 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 epsilon4 allele were associated with a 4.1-fold (95% CI, 2.2-7.7) increased risk of dementia as compared to the epsilon3/epsilon3 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 epsilon2 and epsilon4; 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 epsilon4 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 epsilon2/epsilon3/epsilon4 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. SN - 0148-7299 UR - https://www.unboundmedicine.com/medline/citation/11807900/Association_of_APOE_epsilon2/epsilon3/epsilon4_and_promoter_gene_variants_with_dementia_but_not_cardiovascular_mortality_in_old_age_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=2002&volume=107&issue=3&spage=201 DB - PRIME DP - Unbound Medicine ER -