Journal
HUMAN HEREDITY
Volume 61, Issue 3, Pages 157-165Publisher
KARGER
DOI: 10.1159/000094141
Keywords
case-control association analysis; environmental risk factor; epidemiologic approaches; gene-environment interaction; genotype; macular degeneration
Categories
Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR020278] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R01EY012203, R01EY011309] Funding Source: NIH RePORTER
- NCRR NIH HHS [U54 RR 020278] Funding Source: Medline
- NEI NIH HHS [R01 EY 12203, R01 EY 11309] Funding Source: Medline
Ask authors/readers for more resources
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. Copyright (c) 2006 S. Karger AG, Basel.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available