Cited by 834Retinal Diseases and TreatmentsComplement system in diseasesOcular Diseases and Behçet’s Syndrome

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Complement C3 Variant and the Risk of Age-Related Macular Degeneration

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Yates, John R.W., Sepp, Tiina, Matharu, Baljinder K., Khan, Jane C., Thurlby, Deborah A., Shahid, Humma, Clayton, David G., Hayward, Caroline, Morgan, Joanne, Wright, Alan F., Armbrecht, Ana Maria, Dhillon, Baljean, Deary, Ian J., Redmond, Elizabeth, Bird, Alan C., Moore, Anthony T.·2007·New England Journal of Medicine

DOI 10.1056/nejmoa072618

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Abstract

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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Friedrich, U., Fritsche, L. G., & Weber, B. H. F. (2011) · Springer eBooks · doi:10.1007/978-3-642-20870-6_2
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Haim, L. N. B., Duncan, J. L., & Zayit‐Soudry, S. (2021) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0029296
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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: Yates, John R.W.
Clayton, David G.
Hayward, Caroline
Dhillon, Baljean
Deary, Ian J.
Bird, Alan C.
Moore, Anthony T.
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
DOI: 10.1056/nejmoa072618
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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Complement C3 Variant and the Risk of Age-Related Macular Degeneration

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