Opin vísindi

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

Show simple item record

dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Wolters, Frank J.
dc.contributor.author Yang, Qiong
dc.contributor.author Biggs, Mary L.
dc.contributor.author Jakobsdottir, Johanna
dc.contributor.author Li, Shuo
dc.contributor.author Evans, Daniel S.
dc.contributor.author Bis, Joshua C.
dc.contributor.author Harris, Tamara B.
dc.contributor.author Vasan, Ramachandran S.
dc.contributor.author Zilhao, Nuno R.
dc.contributor.author Ghanbari, Mohsen
dc.contributor.author Ikram, M. Arfan
dc.contributor.author Launer, Lenore
dc.contributor.author Psaty, Bruce M.
dc.contributor.author Tranah, Gregory J.
dc.contributor.author Kulminski, Alexander M.
dc.contributor.author Gudnason, Vilmundur
dc.contributor.author Seshadri, Sudha
dc.date.accessioned 2020-08-13T11:16:50Z
dc.date.available 2020-08-13T11:16:50Z
dc.date.issued 2019-07-29
dc.identifier.citation Wolters FJ, Yang Q, Biggs ML, Jakobsdottir J, Li S, Evans DS, et al. (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
dc.identifier.issn 1932-6203
dc.identifier.uri https://hdl.handle.net/20.500.11815/1986
dc.description Publisher's version (útgefin grein)
dc.description.abstract Background Apolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-e4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-e2 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-e2, with survival in the population. Results During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-e3 carriers, APOE-e2 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-e4 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-e2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-e4 (HR 1.52,1.37- 1.70). After censoring for dementia, effect estimates remained similar for APOE-e2 (HR 0.95,0.90-1.01), but attenuated for APOE-e4 (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 e2 versus e33: -17.1(-18.1-16.0), and e4 versus e33: +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-e3, APOE-e2 is associated with prolonged survival, whereas mortality risk is increased for APOE-e4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-e2 in health and disease.
dc.description.sponsorship Infrastructure for the CHARGE Consortium members in this grant is supported in part by the National Heart, Lung, and Blood Institute (NHLBI, http://www.nhlbi.nih.gov) grant HL105756 (Psaty) and AG033193 (Seshadri). This work was also supported by a grant from the Consortium to Study the Genetics of Longevity (U19AG023122; PI Cummings; subproject title ‘APOE2 Genotype in Longevity and Healthy Aging’, PI: Seshadri). Detailed funding information for all studies that contributed to this work are provided in the online Appendix funding section (S5 Supporting information). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.format.extent e0219668
dc.language.iso en
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartofseries Plos One;14(7)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Apolipoprotein E
dc.subject Glycoprotein
dc.subject Lipid
dc.subject Lipoprotein
dc.subject Erfðarannsóknir
dc.subject Fituefni
dc.subject Prótín
dc.title The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE)
dc.type info:eu-repo/semantics/article
dcterms.license This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.version Peer Reviewed
dc.identifier.journal Plos One
dc.identifier.doi 10.1371/journal.pone.0219668
dc.relation.url http://dx.plos.org/10.1371/journal.pone.0219668
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

Files in this item

This item appears in the following Collection(s)

Show simple item record