Complement Factor H Increases Risk for Atrophic Age-Related Macular Degeneration
Received 17 October 2005; accepted 2 February 2006. published online 06 July 2006.
Objective
To determine if the complement factor H gene (CFH) determines risk for development of geographic atrophy (GA).
Design
Retrospective case–control study.
Participants and Controls
The independent case–control data set contained 647 age-related macular degeneration (AMD) cases (grades 3, 4, or 5) and 163 controls (grades 1 or 2).
Methods
To determine if CFH had any effect on determining risk for development of GA in an independent case–control data set of 647 AMD cases and 163 controls, the rs1061170 single-nucleotide polymorphism was tested for association, separating grades and analyzing them independently against the controls. Odds ratios were calculated using standard logistic regression models.
Main Outcome Measures
The outcome variable was AMD affection status, and genotypes were coded according to a log-additive model.
Results
There were 407 grade 5, 107 grade 4, 133 grade 3, 35 grade 2, and 128 grade 1 individuals. There was significant association with AMD when comparing grades 3, 4, and 5 versus the controls. The highest odds ratio was obtained when analyzing the grade-4 cases versus the grade-1 controls (OR = 3.217, P<0.0001).
Conclusions
Our results indicate that CFH increases the risk of developing GA (grade 4) as well as neovascular (grade 5) and milder (grade 3) disease. Although neovascular disease is responsible for the majority of severe vision loss with AMD, GA is also a significant cause of vision loss, and without effective treatment. Therefore, an attempt to clarify its pathogenesis is of the utmost importance.
1Duke University Eye Center, Durham, North Carolina.
ABSTRACT