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

TitleThe impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).
Publication TypeJournal Article
Year of Publication2019
AuthorsWolters FJ, Yang Q, Biggs ML, Jakobsdottir J, Li S, Evans DS, Bis JC, Harris TB, Vasan RS, Zilhao NR, Ghanbari M, M Ikram A, Launer L, Psaty BM, Tranah GJ, Kulminski AM, Gudnason V, Seshadri S
Corporate AuthorsE2-CHARGE investigators
JournalPLoS One
Date Published2019

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.

Pubmed Link
Alternate JournalPLoS ONE
PubMed ID31356640
PubMed Central IDPMC6663005
Grant ListU01 AG023712 / AG / NIA NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
U19 AG023122 / AG / NIA NIH HHS / United States
R01 AG049607 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
R01 AG033040 / AG / NIA NIH HHS / United States
R01 AG031287 / AG / NIA NIH HHS / United States

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