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D. Smailhodzic, S. Liakopoulos, B. J. Klevering, C. J. F. Boon, B. Kirchhof, M. R. Daha, C. C. W. Klaver, A. I. Den Hollander, C. B. Hoyng; Evaluation of Serum Complement Levels in Age-Related Macular Degeneration (amd). Invest. Ophthalmol. Vis. Sci. 2010;51(13):6201.
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To measure the concentration of various components of the complement cascade in patients with age-related macular degeneration (AMD) compared to age-matched control individuals. To evaluate the influence of 12 single nucleotide polymorphism (SNP) genotypes on the serum complement levels.
Two hundred advanced stage AMD patients and 150 controls of similar age and gender were selected from EUGENDA, a multicentre database for clinical and molecular analysis of AMD. Hemolytic complement assays (AP50, CP50, MBL50), complement components (C3, CFB, CFI and CFH) and activation fragments (C3d, C5a, SC5b-9) were analyzed in serum and plasma. DNA samples were genotyped for 12 SNPs in 9 genes, previously associated with AMD: CFH, CFB, C3, ARMS2, TLR3, TLR4, SERPING1, ABCA4 and APOE. Correlations between complement biomarkers and genotype, age, gender, smoking, and body mass index were evaluated.
Plasma markers of complement activation fragments (C3d, p<0.0001 and C5a, p<0.0001) were significantly elevated in AMD patients. Interestingly, there was no significant difference in the level of the terminal complex SC5b-9 between AMD and controls (p=0.66). Enzyme precursor factor B was also detectable at higher levels in AMD patients (p=0.0003). Increased activation of the alternative pathway appeared to be the primary cause of the increase in complement levels (p=0.0003). There was no significant difference in the activity of the classical pathway (p=0.56) and the lectin pathway (p=0.25) between AMD patients and controls. The CFH genotype had the most prominent effect on complement activation fragments (C3d and C5a) in AMD patients.
This study confirms that ongoing low level activation of the alternative pathway of the complement system is associated with AMD.
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