Abstract
BackgroundAge-related macular degeneration (AMD), the leading cause of blindness in the Western world, is a complex disease that affects people over 50 years old. The complement factor H (CFH) gene has been repeatedly shown to be a major factor in determining susceptibility to the advanced form of the condition. We aimed to better understand the functional role of this gene in the AMD disease process and assess whether it is associated with earlier forms of the disease.Methodology/Principal FindingsWe genotyped SNPs at the CFH gene locus in three independent populations with AMD: (a) extended families where at least 3 family members had AMD; (b) sporadic cases of advanced AMD and (c) cases from the Age-Related Eye Disease Study (AREDS). We investigated polymorphisms and haplotypes in and around the CFH gene to assess their role in AMD. CFH is associated with early/intermediate and advanced AMD in both familial and sporadic cases. In our populations, the CFH SNP, rs2274700, is most strongly associated with AMD and when incorporated into a haplotype with the Y402H SNP and rs1061147, the strongest association is observed (p<10−9).Conclusions/SignificanceOur results, reproduced in three populations that represent the spectrum of AMD cases, provide evidence that the CFH gene is associated with drusen as well as with advanced AMD. We also identified novel susceptibility and protective haplotypes in the AMD populations.
Highlights
Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world.[1]
We present the results of analyses of 3 populations with AMD: extended families genetically enriched for their predisposition to the disease, sporadic cases of advanced AMD, and the Age-Related Eye Disease Study (AREDS) cohort
The complement factor H (CFH) risk allele rs1061170 ‘C’ and AMD was strongly associated with advanced AMD status in each of the three cohorts: Academic Editor: Derek Gordon, Rutgers University, United States of America
Summary
Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world.[1] The hallmark of AMD is the progressive accumulation of drusen (sub-retinal yellow deposits) at the macula, that portion of the central retina specialized for fine visual tasks. We genotyped SNPs at the CFH gene locus in three independent populations with AMD: (a) extended families where at least 3 family members had AMD; (b) sporadic cases of advanced AMD and (c) cases from the Age-Related Eye Disease Study (AREDS). Our results, reproduced in three populations that represent the spectrum of AMD cases, provide evidence that the CFH gene is associated with drusen as well as with advanced AMD. We identified novel susceptibility and protective haplotypes in the AMD populations
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