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Complement C3 Variant and the Risk of Age-Related Macular Degeneration
Open accessAbstract
BACKGROUND: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis. METHODS: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls. RESULTS: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9x10(-5)) and the Scottish group (244 cases and 351 controls, P=5.0x10(-5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%. CONCLUSIONS: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease.
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In the citing paper
“the fast migrating allotype (C3F), has been reported to be strongly associated with AMD in a study from English and Scottish populations (Yates et al., 2007).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Yates et al., 2007
In the citing paper
“We further confirmed the association with family history of AMD, consistent with the growing recognition of major genes involved in AMD (e.g., complement factor H and C3, LOCS 3877, HTRA 1) [21,83-86].”
From Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis (2010) · cites this paper as [86]
In the citing paper
“Genes in the complement pathway4–11 and a region of chromosome 10 12,13 have now been implicated as the major genetic contributors to disease.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [7]
In the citing paper
“These include complement 2 (C2) and/or complement factor B (CFB) (56), complement 3 (C3) (170), and complement factor I (CFI) (44).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [170]
In the citing paper
“The complement system may indeed have an important role in the pathogenesis of age-related macular degeneration, since other factors such as factor B and complement components C2 and C3 are also associated with age-related macular degeneration.66,67”
From Age-related macular degeneration (2008) · cites this paper as [67]
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Metadata
- Authors
- Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., & Moore, A. T.
- Affiliations
- University of Cambridge (GB)
- MRC Human Genetics Unit (GB)
- Princess Alexandra Eye Pavilion (GB)
- University of Edinburgh (GB)
- University College London (GB)
- Moorfields Eye Hospital (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2007-08-09
- Volume
- 357
- Issue
- 6
- Pages
- 553-561
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2105479207
- Cited by
- 829
- References
- 41
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 30 · 2023: 22 · 2022: 27 · 2021: 30 · 2020: 28 · 2019: 25 · 2018: 25 · 2017: 33 · 2016: 36 · 2015: 52 · 2014: 57 · 2013: 66 · 2012: 81
- FWCI
- 63.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Pfizer
- Wellcome Trust
- Moorfields Eye Hospital NHS Foundation Trust
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, complement C3, single nucleotide polymorphisms, complement activation, genetic susceptibility, population attributable risk, pathogenesis
- MeSH terms
- Aged, Complement C3, Complement C5, Female, Genotype, Humans, Macular Degeneration, Male, Logistic Models, Odds Ratio, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Protein Structure, Quaternary
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