Genetic Association of Apolipoprotein E with Age-Related Macular Degeneration
Open accessAbstract
Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic-association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam Study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2. 82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.
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Association has been demonstrated with several additional loci, each providing an entry-point into AMD biology and potential therapeutic targets.
“Association has also been demonstrated with several additional loci14–20, each providing an entry-point into AMD biology and potential therapeutic targets.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [14]
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“Based upon this fact, Klaver et al. have speculated that an active biosynthesis of ApoE is required to support the high rate of photoreceptor renewal in the macular region (Klaver et al., 1998).”
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Risk factors for age‐related maculopathy in a 14‐year follow‐up study: the Copenhagen City Eye Study
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- Authors
- Klaver, C. C. W., Kliffen, M., van Duijn, C. M., Hofman, A., Cruts, M., Grobbee, D. E., van Broeckhoven, C., & de Jong, P. T. V. M.
- Affiliations
- Erasmus MC (NL)
- University of Antwerp (BE)
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 63
- Issue
- 1
- Pages
- 200-206
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1377225
- OpenAlex
- W2137792435
- Cited by
- 498
- References
- 55
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 15 · 2023: 12 · 2022: 26 · 2021: 13 · 2020: 10 · 2019: 7 · 2018: 15 · 2017: 11 · 2016: 14 · 2015: 19 · 2014: 16 · 2013: 19 · 2012: 25
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Ministry of Health
- Ministry of Education
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Landelijke Stichting voor Blinden en Slechtzienden
- Stichting Blinden-Penning
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- age-related macular degeneration, apolipoprotein E, APOE polymorphism, genetic susceptibility, APOE ε4, APOE ε2 allele, drusen, basal laminar deposits, macula, Rotterdam Study
- MeSH terms
- Aged, Alleles, Apolipoproteins E, Genotype, Humans, Immunochemistry, Macula Lutea, Macular Degeneration, Middle Aged, Netherlands, Polymorphism, Genetic, Risk Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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