BACKGROUND:
Age-related macular degeneration (AMD) is a
prevalent cause of
blindness in Western societies. Variants in the genes encoding
complement factor H (CFH), complement component 3 (C3) and
age-related maculopathy susceptibility 2 (
ARMS2) have repeatedly been shown to confer significant risks for AMD; however, their role in disease progression and thus their potential relevance for interventional therapeutic approaches remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here, we analyzed association between variants in CFH, C3 and
ARMS2 and disease progression of geographic
atrophy (GA) due to AMD. A quantitative
phenotype of disease progression was computed based on longitudinal observations by fundus
autofluorescence imaging. In a subset of 99 cases with pure bilateral GA, variants in CFH (Y402H), C3 (R102G), and
ARMS2 (A69S) are associated with disease (P = 1.6x10(-9), 3.2x10(-3), and P = 2.6x10(-12), respectively) when compared to 612 unrelated healthy control individuals. In cases,
median progression rate of GA over a
mean follow-up period of 3.0 years was 1.61 mm(2)/year with high concordance between fellow
eyes. No association between the progression rate and any of the
genetic risk variants at the three loci was observed (P>0.13). CONCLUSIONS/SIGNIFICANCE: This study confirms that variants at CFH, C3, and
ARMS2 confer significant risks for GA due to AMD. In contrast, our data indicate no association of these variants with disease progression which may have important implications for future treatment strategies. Other, as yet unknown susceptibilities may influence disease progression.
