Association of APOE genotype with carotid atherosclerosis in men and women
Open accessAbstract
The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm). The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.
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Increased levels of atherosclerosis associated with apoE4 could have detrimental effects on brain function through decreased blood flow and altered metabolic properties.
“As a result, increased levels of atherosclerosis associated with apoE4 (Elosua et al., 2004; Graner et al., 2008) could have detrimental effects on brain function through decreased blood flow and altered metabolic properties.”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Elosua et al., 2004
The Discussion and Conclusion report higher internal carotid artery intima-media thickness associated with APOE4 only in men with diabetes. The Discussion also says the study found no significant overall association between the E4 allele and carotid atherosclerosis, so the citing sentence omits an important qualification. Its proposed effects on brain function are the citing authors’ inference, not the part supported by this citation. (LLM, conf=0.88)
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Cites
O'Leary, D. H., Polak, J. F., Kronmal, R. A., Manolio, T. A., Burke, G. L., & Wolfson, S. K. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901073400103 · Cited by 4,685 · 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
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- [2]2. Dallongeville, J. ∙ Lussier-Cacan, S. ∙ Davignon, J. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis J. Lipid Res. 1992; 33:447-454
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The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
the CARDIoGRAM Consortium, Bis, J. C., Kavousi, M., Franceschini, N., Isaacs, A., Abecasis, G. R., Schminke, U., Post, W. S., Smith, A. V., Cupples, L. A., et al. (2011) · Nature Genetics · doi:10.1038/ng.920 · Cited by 212 · see citing works
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- Authors
- Elosua, R., Ordovas, J. M., Cupples, L. A., Fox, C. S., Polak, J. F., Wolf, P. A., D’Agostino, R. A., & O’Donnell, C. J.
- Affiliations
- Boston University (US)
- Brigham and Women's Hospital (US)
- National Institutes of Health (US)
- Corresponding author
- O’Donnell, Christopher J.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 45
- Issue
- 10
- Pages
- 1868-1875
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2136392032
- Cited by
- 101
- References
- 2
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 3 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 8
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (n01hc25195-41-0-1)
- National Heart, Lung, and Blood Institute (HL54776, N01‐HC25195, R01HL054776)
- National Institute of Neurological Disorders and Stroke (5R01 NS 17950-22, R01NS017950)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- APOE genotype, carotid atherosclerosis, carotid intima-media thickness, carotid artery stenosis, APOE ε4, ApoE2 allele, sex differences, diabetes mellitus, cardiovascular risk factors, internal carotid artery, Framingham Offspring Study
- MeSH terms
- Apolipoproteins E, Arteriosclerosis, Carotid Artery Diseases, Female, Gene Frequency, Genotype, Humans, Male, Sex Factors, Ultrasonography, Tunica Intima, Diabetes Complications
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