Skip to main content

The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).

Publication ,  Journal Article
Wolters, FJ; Yang, Q; Biggs, ML; Jakobsdottir, J; Li, S; Evans, DS; Bis, JC; Harris, TB; Vasan, RS; Zilhao, NR; Ghanbari, M; Ikram, MA ...
Published in: PloS one
January 2019

Apolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-ε2 allele on diseases in the elderly and survival remains elusive.We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-ε2, with survival in the population.During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1*10-2), whereas APOE-ε4 carriers were at increased risk of death (HR 1.17,1.12-1.21; P = 2.8*10-16). APOE was associated with mortality risk in a dose-dependent manner, with risk estimates lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). After censoring for dementia, effect estimates remained similar for APOE-ε2 (HR 0.95,0.90-1.01), but attenuated for APOE-ε4 (HR 1.07,1.01-1.12). Results were broadly similar across cohorts, and did not differ by age or sex. APOE genotype was associated with baseline lipid fractions (e.g. mean difference(95%CI) in LDL(mg/dL) for ε2 versus ε33: -17.1(-18.1-16.0), and ε4 versus ε33: +5.7(4.8;6.5)), but the association between APOE and mortality was unaltered after adjustment for baseline LDL or cardiovascular disease. Given the European ancestry of the study population, results may not apply to other ethnicities.Compared with APOE-ε3, APOE-ε2 is associated with prolonged survival, whereas mortality risk is increased for APOE-ε4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-ε2 in health and disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2019

Volume

14

Issue

7

Start / End Page

e0219668

Related Subject Headings

  • Survival Analysis
  • Meta-Analysis as Topic
  • Male
  • Lipids
  • Humans
  • Heterozygote
  • Genotype
  • General Science & Technology
  • Female
  • Cohort Studies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wolters, F. J., Yang, Q., Biggs, M. L., Jakobsdottir, J., Li, S., Evans, D. S., … E2-CHARGE investigators, . (2019). The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE). PloS One, 14(7), e0219668. https://doi.org/10.1371/journal.pone.0219668
Wolters, Frank J., Qiong Yang, Mary L. Biggs, Johanna Jakobsdottir, Shuo Li, Daniel S. Evans, Joshua C. Bis, et al. “The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).PloS One 14, no. 7 (January 2019): e0219668. https://doi.org/10.1371/journal.pone.0219668.
Wolters FJ, Yang Q, Biggs ML, Jakobsdottir J, Li S, Evans DS, et al. The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE). PloS one. 2019 Jan;14(7):e0219668.
Wolters, Frank J., et al. “The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).PloS One, vol. 14, no. 7, Jan. 2019, p. e0219668. Epmc, doi:10.1371/journal.pone.0219668.
Wolters FJ, Yang Q, Biggs ML, Jakobsdottir J, Li S, Evans DS, Bis JC, Harris TB, Vasan RS, Zilhao NR, Ghanbari M, Ikram MA, Launer L, Psaty BM, Tranah GJ, Kulminski AM, Gudnason V, Seshadri S, E2-CHARGE investigators. The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE). PloS one. 2019 Jan;14(7):e0219668.

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2019

Volume

14

Issue

7

Start / End Page

e0219668

Related Subject Headings

  • Survival Analysis
  • Meta-Analysis as Topic
  • Male
  • Lipids
  • Humans
  • Heterozygote
  • Genotype
  • General Science & Technology
  • Female
  • Cohort Studies