Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration
Abstract
Age-related macular degeneration (AMD) impairs vision for approximately 7.5 million Americans. Both susceptibility variants and protective haplotypes in the complement factor H (CFH) gene modulate risk for AMD. Recently, deletion of the 'CFH-related' genes CFHR1 and CFHR3 was found to be segregating with a particular CFH haplotype, which reduced the risk of AMD. We tested the deletion for association in a Caucasian population of 780 cases and 265 controls and examined its effect in the context of known AMD risk factors. The deletion did not segregate perfectly with any one SNP, as previously suggested. CFH haplotype P2 was the most frequent haplotype in deletion homozygotes (47%), and the majority (14/16) of these individuals were homozygous for the non-risk allele of Y402H. Overall, deletion homozygosity was significantly more frequent in controls than cases (2.6% controls, 0.8% cases, P = 0.025, OR = 0.29, 95% CI = 0.10-0.86). After controlling for age, Y402H, smoking and LOC387715 A69S, the protective effect of the deletion was no longer statistically significant (P = 0.27). However, using a CFH haplotype that all deletion homozygotes share as a surrogate for the deletion, this marker remained modestly associated with AMD after adjustment for known risk factors (OR = 0.63, 95% CI 0.39-1.04, P = 0.07). Therefore, deletion of CFHR1 and CFHR3 may account for a small portion of the protection from AMD associated with particular haplotypes in CFH. The presence of protective haplotypes in CFH that do not carry the deletion, suggests that other protective variants in this region have yet to be discovered.
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Deletions in two genes near CFH, CFHR1 and CFHR3, have been associated with reduced risk of AMD.
“In addition to simple sequence changes, deletions in two genes near CFH, CFHR1 and CFHR3, have been associated with reduced risk of AMD (75, 143) (see Figure 5).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [143]
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- Authors
- Spencer, K. L., Hauser, M. A., Olson, L. M., Schmidt, S., Scott, W. K., Gallins, P., Agarwal, A., Postel, E. A., Pericak-Vance, M. A., & Haines, J. L.
- Affiliations
- Vanderbilt University Medical Center (US)
- Duke University (US)
- University of Miami (US)
- Corresponding author
- Haines, Jonathan L.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-12-15
- Volume
- 17
- Issue
- 7
- Pages
- 971-977
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2139165925
- Cited by
- 102
- References
- 25
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 9 · 2015: 3 · 2014: 6 · 2013: 10 · 2012: 7
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R03EY015216, EY015216, EY12118)
- National Center for Research Resources (M01RR000095, M01-RR-00095)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- age-related macular degeneration, complement factor H, LOC387715, genetic susceptibility, protective haplotypes, genetic association
- MeSH terms
- Aged, Aged, 80 and over, Analysis of Variance, Base Sequence, Blood Proteins, Chromosomes, Human, Pair 1, Complement C3b Inactivator Proteins, Female, Haplotypes, Homozygote, Humans, Macular Degeneration, Male, Middle Aged, Linkage Disequilibrium, Logistic Models, Polymerase Chain Reaction, Gene Deletion, Polymorphism, Single Nucleotide
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