Independent effects of complement factor H Y402H polymorphism and cigarette smoking on risk of age-related macular degeneration.
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).


METHODS
Retrospective case-control study.


METHODS
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.


METHODS
Age-related macular degeneration affection status.


RESULTS
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.


CONCLUSIONS
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.
Scott
William K
WK
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA. bill.scott@duke.edu
Schmidt
Silke
S
Hauser
Michael A
MA
Gallins
Paul
P
Schnetz-Boutaud
Nathalie
N
Spencer
Kylee L
KL
Gilbert
John R
JR
Agarwal
Anita
A
Postel
Eric A
EA
Haines
Jonathan L
JL
Pericak-Vance
Margaret A
MA
D000368:Aged; D016022:Case-Control Studies; D020256:Choroidal Neovascularization / Q000209:etiology; D017242:Complement Factor H / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
C493495:CFH protein, human; D017242:Complement Factor H