부산대학교 도서관

The common apolipoprotein E (APOE) alleles ɛ2, ɛ3, and ɛ4 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 ɛ4 allele were associated with a 4.1-fold (95% CI, 2.2–7.7) increased risk of dementia as compared to the ɛ3/ɛ3 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 ɛ2 and ɛ4; 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 ɛ4 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 ɛ2/ɛ3/ɛ4 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.