Racial Differences in the Association Between Apolipoprotein E Risk Alleles and Overall and Total Cardiovascular Mortality Over 18 Years
Open accessAbstract
Objectives: To examine the difference in the association between apolipoprotein ( APO )E allele and overall and cardiovascular mortality between African Americans ( AA s) and European Americans ( EA s). Design: Longitudinal, cohort study of 18 years. Setting: Biracial urban US population sample. Participants: 4,917, 68% AA and 32% EA. Measurements: APOE genotype and mortality based on National Death Index. Results: A higher proportion of AA s than of EA s had an APOE ε 2 allele ( ε 2 ε 2/ ε 2 ε 3/ ε 2 ε 4; 22% vs 13%) and an APOE ε 4 allele ( ε 3 ε 4/ ε 4 ε 4; 33% vs 24%). After adjusting for known risk factors, the risk of mortality was 19% less with the APOE ε 2 allele (hazard ratio ( HR ) = 0.81, 95% confidence interval ( CI ) = 0.76–0.87), and the risk of cardiovascular mortality was 35% less ( HR = 0.65, 95% CI = 0.58–0.76) than with the ε 3 ε 3 allele. The risk of mortality was 10% greater with the APOE ε 4 allele ( HR = 1.10, 95% CI = 1.04–1.16), and the risk of cardiovascular mortality was 20% greater ( HR = 1.20, 95% CI = 1.07–1.29) than with the ε 3 ε 3 allele. No difference in the association between APOE allele and mortality was observed between AA s and EA s. Conclusion: The APOE ε 4 allele increased the risk of overall and cardiovascular mortality, whereas the APOE ε 2 allele decreased the risk of overall and cardiovascular mortality. There was no racial difference in the association between these alleles and mortality.
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A higher percentage of African Americans have at least one copy of the e4 allele than European American and American Indian people.
“For instance, data show that a higher percentage of African Americans have at least one copy of the e4 allele (see Table 3) than European American and American Indian people.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [93]
The Results section, “Frequency of APOE Alleles in AAs and EAs” (page not provided), reports that 33% of African Americans versus 24% of European Americans had one or more APOE ε4 alleles. The paper compares those two groups but provides no comparison with American Indian people, so that part of the claim is unsupported. (LLM, conf=0.90)
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1993) · doi:10.1007/978-1-4899-4541-9 · Cited by 21,230 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,803 · see citing works
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,003 · see citing works
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.
Hixson, J., & Vernier, D. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43176-1 · Cited by 2,933 · see citing works
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Apolipoprotein E genotyping by one-stage PCR
Wenham, P. R., Price, W. H., & Blundell, G. (1991) · The Lancet · doi:10.1016/0140-6736(91)92823-k · Cited by 1,070 · see citing works
Apolipoprotein E Polymorphism and Cardiovascular Disease: A HuGE Review
Eichner, J. E. (2002) · American Journal of Epidemiology · doi:10.1093/aje/155.6.487 · Cited by 796 · see citing works
Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele?
Corbo, R. M., & Scacchi, R. (1999) · Annals of Human Genetics · doi:10.1046/j.1469-1809.1999.6340301.x · Cited by 653 · see citing works
Albert, M., Smith, L. A., Scherr, P. A., Taylor, J. O., Evans, D. A., & Funkenstein, H. H. (1991) · International Journal of Neuroscience · doi:10.3109/00207459109150691 · Cited by 495 · see citing works
Self-citationApolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study
Wilson, P. W. F. (1994) · JAMA · doi:10.1001/jama.1994.03520210050031 · Cited by 468 · see citing works
Cognitive activity and incident AD in a population-based sample of older persons
Wilson, R. S., Bennett, D. A., Bienias, J. L., Aggarwal, N. T., Mendes de Leon, C. F., Morris, M. C., Schneider, J. A., & Evans, D. A. (2002) · Neurology · doi:10.1212/01.wnl.0000036905.59156.a1 · Cited by 456 · see citing works
Self-citationRates of dementia in three ethnoracial groups
Gurland, B. J., Wilder, D. E., Lantigua, R., Stern, Y., Chen, J., Killeffer, E. H. P., & Mayeux, R. P. (1999) · International Journal of Geriatric Psychiatry · doi:10.1002/(sici)1099-1166(199906)14:6 · Cited by 417 · see citing works
Evans, D. A., Bennett, D. A., Wilson, R. S., Bienias, J. L., Morris, M. C., Scherr, P. A., Hebert, L. E., Aggarwal, N., Beckett, L. A., Joglekar, R., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.2.185 · Cited by 370 · see citing works
Self-citationCognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia
Rajan, K. B., Wilson, R. S., Weuve, J., Barnes, L. L., & Evans, D. A. (2015) · Neurology · doi:10.1212/wnl.0000000000001774 · Cited by 260 · see citing works
Self-citationCognitive Activity in Older Persons From a Geographically Defined Population
Wilson, R. S., Bennett, D. A., Beckett, L. A., Morris, M. C., Gilley, D. W., Bienias, J. L., Scherr, P. A., & Evans, D. A. (1999) · The Journals of Gerontology Series B · doi:10.1093/geronb/54b.3.p155 · Cited by 232 · see citing works
Self-citationSkoog, I. G., Hesse, C., Aevarsson, Ó., Landahl, S., Wahlström, J., Fredman, P., & Blennow, K. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.64.1.37 · Cited by 143 · see citing works
Diagnosis and assessment of Alzheimer's disease in diverse populations
Dilworth‐Anderson, P., Hendrie, H. C., Manly, J. J., Khachaturian, A. S., & Fazio, S. (2008) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2008.03.001 · Cited by 139 · see citing works
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · see citing works
<i>APOE ε4 does not predict mortality, cognitive decline, or dementia in the oldest old</i>
Juva, K., Verkkoniemi, A., Viramo, P., Polvikoski, T., Kainulainen, K., Kontula, K., & Sulkava, R. (2000) · Neurology · doi:10.1212/wnl.54.2.412 · Cited by 108 · see citing works
APOE-related mortality: effect of dementia, cardiovascular disease and gender.
Rosvall, L., Rizzuto, D., Wang, H.-X., Winblad, B., Graff, C., & Fratiglioni, L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.12.003 · Cited by 104 · see citing works
Epidemiology and burden of cardiovascular disease
Watkins, L. O. (2004) · Clinical Cardiology · doi:10.1002/clc.4960271503 · Cited by 103 · see citing works
Soerensen, M., Dato, S., Tan, Q., Thinggaard, M., Kleindorp, R., Beekman, M., Suchiman, H. E. D., Lindahl‐Jacobsen, R., McGue, M. K., Stevnsner, T., et al. (2012) · AGE · doi:10.1007/s11357-011-9373-7 · Cited by 95 · see citing works
Wilson, P. W. F., Myers, R. H., Larson, M. G., Ordovás, J. M., Wolf, P. A., & Schaefer, E. J. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)92270-f · Cited by 93 · see citing works
Prasher, V. P., Sajith, S. G., Rees, S. D., Patel, A., Tewari, S., Schupf, N., & Zigman, W. B. (2008) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2039 · Cited by 89 · see citing works
Mortality differences by APOE genotype estimated from demographic synthesis
Ewbank, D. C. (2002) · Genetic Epidemiology · doi:10.1002/gepi.0164 · Cited by 82 · see citing works
Association of Cognitive Functioning, Incident Stroke, and Mortality in Older Adults
Rajan, K. B., Aggarwal, N. T., Wilson, R. S., Everson‐Rose, S. A., & Evans, D. A. (2014) · Stroke · doi:10.1161/strokeaha.114.005143 · Cited by 71 · see citing works
Self-citationProtective effect of apoE ∈2 in Alzheimer's disease
Benjamin, R., Leake, A., McArthur, F. K., Ince, P. G., Candy, J., Edwardson, J. A., Morris, C. M., & Bjertness, E. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91804-x · Cited by 67 · see citing works
Lindahl‐Jacobsen, R., Martinussen, T., Christiansen, L., Jeune, B., Andersen‐Ranberg, K., Vaupel, J. W., & Christensen, K. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00626.x · Cited by 66 · see citing works
Heijmans, B. T., Slagboom, P. E., Gussekloo, J., Droog, S., Lagaay, A. M., Kluft, C., Knook, D. L., & Westendorp, R. G. J. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10142 · Cited by 50 · see citing works
Beydoun, M. A., Beydoun, H. A., Kaufman, J. S., An, Y., Resnick, S. M., O’Brien, R., Ferrucci, L., & Zonderman, A. B. (2013) · Journal of the American Geriatrics Society · doi:10.1111/jgs.12156 · Cited by 39 · see citing works
Nygaard, M., Lindahl‐Jacobsen, R., Soerensen, M., Mengel‐From, J., Andersen‐Ranberg, K., Jeune, B., Vaupel, J. W., Tan, Q., Christiansen, L., & Christensen, K. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.04.018 · Cited by 31 · see citing works
Effects of the APOE 2 Allele on Mortality and Cognitive Function in the Oldest Old
Lindahl‐Jacobsen, R., Tan, Q., Mengel‐From, J., Christensen, K., Nebel, A., & Christiansen, L. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls192 · Cited by 29 · see citing works
Rajan, K. B., Wilson, R. S., Skarupski, K. A., de Leon, C. F. M., & Evans, D. A. (2014) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000029 · Cited by 28 · see citing works
Self-citationBody Mass Index, Cognition, Disability, APOE Genotype, and Mortality: The “Treviso Longeva” Study
Gustafson, D., Mazzuco, S., Ongaro, F., Antuono, P., Forloni, G., Albani, D., Gajo, G., Durante, E., Caberlotto, L., Zanardo, A., et al. (2011) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31823031a4 · Cited by 25 · see citing works
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- Authors
- Rajan, K. B., Barnes, L. L., Wilson, R. S., McAninch, E. A., Weuve, J., Sighoko, D., & Evans, D. A.
- Affiliations
- Rush University Medical Center (US)
- Boston University (US)
- Corresponding author
- Rajan, Kumar B.
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 2017-09-12
- Volume
- 65
- Issue
- 11
- Pages
- 2425-2430
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- PMC
- PMC6201232
- OpenAlex
- W2756039380
- Cited by
- 59
- References
- 39
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 10 · 2021: 11 · 2020: 2 · 2019: 6 · 2018: 3
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 AG051635, R01 AG11101)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- apolipoprotein E, APOE ε4, APOE ε2 allele, cardiovascular mortality, all-cause mortality, racial differences, African Americans, European Americans, genetic risk factors
- MeSH terms
- Aged, Aged, 80 and over, Apolipoproteins E, Black or African American, Cardiovascular Diseases, Female, Humans, Longitudinal Studies, Male, Risk Factors, Incidence, Confidence Intervals, Odds Ratio, Genetic Predisposition to Disease, White People, Genetic Association Studies
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