Complement Component C3 and Risk of Age-Related Macular Degeneration
Abstract
Objective To explore the association between polymorphisms in the complement component 3 (C3) gene and age-related macular degeneration (AMD), and to investigate the modifying effect of complement factor H (CFH) Y402H, LOC387715 A69S and smoking.Design Pooled data from the prospective, population-based Rotterdam Study (enrolment between 1990 and 1993, and 3 follow-up examinations between September 1, 1993, and December 31, 2004) and an independent case-control study from the Netherlands.Participants The Rotterdam Study comprised a total of 6418 persons aged >or=55 years who had gradable fundus photographs. The case-control study consisted of 357 unrelated AMD patients and 173 control individuals aged >or=55 years.Methods The variants R102G and P314L of the C3 gene, CFH Y402H and LOC387715 A69S, were genotyped in all study participants. Information on cigarette smoking was obtained by interview at baseline.Main outcome measures Early and late stages of prevalent and incident AMD, graded according to the international classification and grading system for AMD.Results We found a population frequency of 0.217 for R102G and 0.211 for P314L in the Rotterdam Study. Both alleles significantly increased the risk of early AMD and all subtypes of late AMD, and this risk seemed to be independent of CFH Y402H, LOC387715 A69S, and smoking. Detailed analysis showed that the haplotype carrying both alleles had the highest frequency difference between cases and controls (P=0.006). We estimated a total population-attributable risk of 14.6%. A meta-analysis of all currently available data yielded a pooled odds ratio (OR) of 1.61 (95% confidence interval [CI], 1.46-1.78) for the R102G allele, and an OR of 1.50 (95% CI, 1.31-1.71) for the P314L allele.Conclusions Our study showed a significant association between variants in the C3 gene and AMD and further highlights the crucial role of the complement pathway in the etiology of AMD.
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We further confirmed the association with family history of AMD.
“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 [85]
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Self-citation
- Authors
- Despriet, D. D. G., van Duijn, C. M., Oostra, B. A., Uitterlinden, A. G., Hofman, A., Wright, A. F., ten Brink, J. B., Bakker, A., de Jong, P. T. V. M., Vingerling, J. R., Bergen, A. A. B., & Klaver, C. C. W.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Erasmus MC (NL)
- MRC Human Genetics Unit (GB)
- Corresponding author
- Vingerling, Johannes R.
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 116
- Issue
- 3
- Pages
- 474-480.e2
- ISSN
- 0161-6420 (ISSN-L)
- OpenAlex
- W2108852798
- Cited by
- 94
- References
- 27
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 8 · 2013: 4 · 2012: 18
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- age-related macular degeneration, complement C3, smoking, complement pathway, genetic susceptibility, haplotypes, population attributable risk, Rotterdam Study, late AMD
- MeSH terms
- Aged, Aged, 80 and over, Chromatography, High Pressure Liquid, Complement C3, Female, Follow-Up Studies, Genotype, Humans, Macular Degeneration, Male, Middle Aged, Prospective Studies, Proteins, Risk Factors, Smoking, Case-Control Studies, Complement Factor H, Polymorphism, Single Nucleotide
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