CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration
Abstract
Objectives: We tested the hypothesis that modifiable lifestyle factors alter the genetic susceptibility associated with a common coding variant in the complement factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly, age-related macular degeneration (AMD). Methods: In this case-control association analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated. AMD status was determined by grading of fundus photographs. Risk factors including cigarette smoking and body mass index (BMI) were assessed and DNA specimens were genotyped for the variant in the CFH gene. Unconditional logistic regression analyses were performed. Attributable risks and multivariable AMD risk scores were calculated. Results: The number of risk alleles for Y402H was associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence interval (CI) 1.8–3.8) for the CT heterozygous genotype and OR 7.4 (4.7–11.8) for the homozygous CC risk genotype, after controlling for demographic and behavioral risk factors. Current cigarette smoking (OR 5.1) and high BMI ≧30 (OR 2.1) were independently related to AMD, controlling for genotype. The association between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR 10.2) conferred the greatest risks. Gene plus environment risk scores provided an area under the receiver operating characteristic (ROC) curve of 0.70–0.75. Conclusions: Genetic and environmental factors are independently related to advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk score identifies a highly susceptible population.
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No definitive gene/gene or gene/environment interaction has yet been found for age-related macular degeneration.
“A few studies have assessed gene/gene interaction as well as gene/environment interaction.73–75 No definitive interaction has yet been found.”
From Age-related macular degeneration (2008) · cites this paper as [75]
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- Authors
- Seddon, J. M., George, S., Rosner, B., & Klein, M. L.
- Affiliations
- Massachusetts Eye and Ear Infirmary (US)
- Harvard University (US)
- Oregon Health & Science University (US)
- Venue
- Human Heredity
- Publisher
- S. Karger AG
- Published
- 2006
- Volume
- 61
- Issue
- 3
- Pages
- 157-165
- ISSN
- 0001-5652 (ISSN-L)
- 1423-0062
- OpenAlex
- W2070050918
- Semantic Scholar
- c16cf2d25d9592b62e2aba0de8cd0d44762fbb89
- Cited by
- 176
- References
- 33
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 8 · 2013: 14 · 2012: 5
- FWCI
- 18.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Heredity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (6u54rr020278-06)
- National Eye Institute (R01-EY12203, R01EY012203, R01 EY 11309, R01EY011309)
- National Center for Research Resources (U54-RR020278)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- age-related macular degeneration, complement factor H, genetic susceptibility, cigarette smoking, body mass index, gene-environment interaction, modifiable lifestyle risk factors, attributable risk, AREDS
- MeSH terms
- Aged, Aged, 80 and over, Aging, Female, Genotype, Humans, Macular Degeneration, Male, Middle Aged, Polymorphism, Genetic, Risk Factors, Smoking, Body Mass Index, Case-Control Studies, Complement Factor H, Genetic Predisposition to Disease
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