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R. Reynolds, M. E. Hartnett, B. Rosner, J. Atkinson, P. Giclas, J. M. Seddon; Plasma Complement Activation Fragments are Associated with AMD Genotypes and Phenotypes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3445.
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Several genes encoding complement system proteins are associated with age-related macular degeneration (AMD). We evaluated whether alterations in plasma proteins responsible for complement activation and regulation are also independentlyassociated with advanced AMD.
From our AMD registry we selected plasma and DNA samples from individuals who progressed to the advanced stages of AMD, including 58 with geographic atrophy (GA) and 62 with neovascular disease (CNV). Subjects without AMD of similar age and gender were included as controls (n=60). Plasma complement proteins and activation fragments were analyzed: Bb, C3, C3a, C5a, CFB, iC3b, SC5b-9, CFI, and CFH. DNA samples were genotyped for seven single nucleotide polymorphisms in six genes previously shown to be associated with AMD: CFB, CFH, C2, C3, CFI, and the LOC387715/HTRA1 gene region. The association of each complement protein with AMD was assessed using logistic regression analysis controlling for age, gender, smoking, body mass index and seven AMD genotypes.
As shown in the table, the highest quartiles of plasma Bb and C5a were significantly associated with advanced AMD compared with the lowest quartile, controlling for age, gender, smoking, and BMI, in models with and without genetic variants. The highest quartile of CFB was associated with advanced AMD when genotype was added to the model. Plasma CFH was inversely associated with advanced AMD in the model without genotypes.
Increased plasma levels of the complement activation fragments Bb and C5a are independently associated with advanced AMD. Results implicate ongoing activation of the alternative complement pathway in AMD pathogenesis.
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