Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: apolipoprotein E gene is a "frailty gene," not a "longevity gene".


Journal Article

We developed a method to estimate genotype-specific average relative mortality risk, R, from genotype distributions in cross-sectional studies of people belonging to different age-groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data from a study of 40-year-old Danish men. Twenty-one percent of the centenarians were epsilon 2-carriers (genotypes epsilon 2 epsilon 2 and epsilon 3 epsilon 2) and 15% were epsilon 4-carriers (genotypes epsilon 4 epsilon 4 and epsilon 4 epsilon 3) compared to 13 and 29%, respectively, of the young men. The R-values were 0.95 (95% CI 0.88 to 1.02) for epsilon 2-carriers and 1.13 (95% CI 1.05 to 1.22) for epsilon 4-carriers, using epsilon 3 epsilon 3- and epsilon 4 epsilon 2 genotypes as reference. Corresponding values for epsilon 4-carriers were obtained by using published data from a French and a Finnish study of centenarians, whereas the values for epsilon 2-carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a "frailty gene." On the other hand, if odds ratios are used to summarize data from studies of this kind, they are more impressive and may propagate the misconception that apoE is a "longevity gene".

Full Text

Duke Authors

Cited Authors

  • Gerdes, LU; Jeune, B; Ranberg, KA; Nybo, H; Vaupel, JW

Published Date

  • October 2000

Published In

Volume / Issue

  • 19 / 3

Start / End Page

  • 202 - 210

PubMed ID

  • 11015124

Pubmed Central ID

  • 11015124

Electronic International Standard Serial Number (EISSN)

  • 1098-2272

International Standard Serial Number (ISSN)

  • 0741-0395

Digital Object Identifier (DOI)

  • 10.1002/1098-2272(200010)19:3<202::aid-gepi2>;2-q


  • eng