The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE)
| Autor: | Qiong Yang, M. Arfan Ikram, Joshua C. Bis, Ramachandran S. Vasan, Lenore J. Launer, Nuno R. Zilhão, Tamara B. Harris, Bruce M. Psaty, Mary L. Biggs, Shuo Li, Daniel S. Evans, Frank J. Wolters, Vilmundur Gudnason, Sudha Seshadri, Mohsen Ghanbari, Johanna Jakobsdottir, Alexander M. Kulminski, Gregory J. Tranah |
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| Přispěvatelé: | Epidemiology |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Heredity Cardiovascular Medicine Biochemistry Cohort Studies Geographical Locations Rotterdam Study 0302 clinical medicine Framingham Heart Study Medicine and Health Sciences education.field_of_study Multidisciplinary Lipids 3. Good health Europe Genetic Mapping Neurology Research Design Cardiovascular Diseases Population study Medicine lipids (amino acids peptides and proteins) Female Cohort study Research Article medicine.medical_specialty Heterozygote Genotype Science Lipoproteins Population Variant Genotypes Lower risk Research and Analysis Methods Apolipoprotein Genes 03 medical and health sciences Apolipoproteins E Meta-Analysis as Topic Internal medicine Mental Health and Psychiatry medicine Genetics Humans education Survival analysis Aged business.industry Biology and Life Sciences Proteins Survival Analysis 030104 developmental biology People and Places Dementia business 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 7, p e0219668 (2019) PLoS One (print), 14(7):e0219668. Public Library of Science |
| ISSN: | 1932-6203 |
| Popis: | BackgroundApolipoprotein 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.MethodsWe 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.ResultsDuring 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.ConclusionCompared 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. |
| Databáze: | OpenAIRE |
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