Complement Factor H Polymorphism, Complement Activators, and Risk of Age-Related Macular Degeneration

Context: The evidence that inflammation is an important pathway in age-related macular degeneration (AMD) is growing. Recent case-control studies demonstrated an association between the complement factor H (CFH) gene, a regulator of complement, and AMD.
Objectives: To assess the associations between the CFH gene and AMD in the general population and to investigate the modifying effect of smoking, serum inflammatory markers, and genetic variation of C-reactive protein (CRP).
Design, Setting, and Participants: Population-based, prospective cohort study of individuals aged 55 years or older (enrollment between March 20, 1990, and July 31, 1993, and 3 follow-up examinations that were performed between September 1, 1993, and December 31, 2004) in Rotterdam, the Netherlands. The CFH Y402H polymorphism was determined in a total of 5681 individuals. Information on smoking, erythrocyte sedimentation rate, CRP serum levels, and haplotypes of the CRP gene were assessed at baseline.
Main Outcome Measures: All severity stages of prevalent and incident AMD, graded according to the international classification and grading system for AMD.