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  3. Medizin - Open Access LMU - Teil 15/22 Podcast
  4. CFH, C3 and ARMS2 are significant risk loci for susceptibility but not for disease progression of geographic atrophy due to AMD.
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. 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).
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.

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„CFH, C3 and ARMS2 are significant risk loci for susceptibility but not for disease progression of geographic atrophy due to AMD.“

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