Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
This study confirms that ongoing low level activation of the alternative pathway of the complement system is associated with AMD.
Keywords: age-related macular degeneration • inflammation • gene screening