Independent Effects of Complement Factor H Y402H Polymorphism and Cigarette Smoking on Risk of Age-Related Macular Degeneration
Received 30 January 2006; accepted 23 August 2006. published online 22 January 2007.
Objective
To examine the potential gene–environment interaction between cigarette smoking and the complement factor H (CFH) T1277C polymorphism, 2 strong risk factors for age-related macular degeneration (AMD).
Design
Retrospective case–control study.
Participants
A university clinic-based sample of 599 people with AMD and 242 controls.
Methods
Standard criteria were used to rate disease severity (grades 1–5) from fundus photographs. Individuals were classified as “ever smokers” or “never smokers” based on self-reported lifetime smoking of at least 100 cigarettes. Intensity of smoking was evaluated by calculating pack-years of smoking, which was analyzed as a continuous variable, and by categorizing individuals as smoking more or less than the median 30 pack-years. T1277C genotypes were determined by sequencing the polymorphic site. Generalized estimating equations were used to analyze the effects of smoking and genotype, controlling for age and gender and adjusting for correlations among related subjects.
Interaction terms between T1277C genotype and smoking variables were not statistically significant, indicating a multiplicative relationship between risk factors. Effects of both T1277C genotype and cigarette smoking were stronger when comparing neovascular (grade 5) AMD with grade 1 controls than when comparing all cases (grades 3–5) with grades 1 to 2 controls.
Conclusion
These results suggest that cigarette smoking and T1277C are independent risk factors for AMD and that both risk factors are associated more strongly with neovascular AMD than all forms of AMD combined.
1Center for Human Genetics, Duke University Medical Center, Durham, North Carolina.
2Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee.
Correspondence to William K. Scott, Ph.D, Associate Professor, Duke Center for Human Genetics, DUMC Box 3445, Durham, NC 27710.
Manuscript no. 2006-130.
This study was supported by the National Institutes of Health/National Eye Institute, Bethesda, Maryland (grant nos. EY12118 [MAP-V], EY15216 [SS]).
ABSTRACT