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Meta-Analysis
. 2011 Nov 11;52(12):8828-34.
doi: 10.1167/iovs.11-7933.

Complement factor D in age-related macular degeneration

Chloe M Stanton  1 , John R W Yates, Anneke I den Hollander, Johanna M Seddon, Anand Swaroop, Dwight Stambolian, Sascha Fauser, Carel Hoyng, Yi Yu, Kanda Atsuhiro, Kari Branham, Mohammad Othman, Wei Chen, Elod Kortvely, Kevin Chalmers, Caroline Hayward, Anthony T Moore, Baljean Dhillon, Marius Ueffing, Alan F Wright
Affiliations
Meta-Analysis

Complement factor D in age-related macular degeneration

Chloe M Stanton et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations.

Methods: Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay.

Results: Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females.

Conclusions: CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis.

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Figures

Figure 1.
Figure 1.
Forest plot summarizing the results of the meta-analysis of association studies between CFD SNP rs3826945 and AMD in three United States AMD case-control series (USA 1–3) and three European case-control series (UK 1–2, and Dutch-German [Nijmegen]). The result of meta-analysis showed a significant association in the combined sexes (OR, 1.11; P = 0.032) and in combined females (OR, 1.18; P = 0.012) but not in males.
Figure 2.
Figure 2.
CNV in the CFD gene in AMD cases and controls showing the proportion of duplicated and deleted genes. The difference between AMD cases and controls was not statistically significant.
Figure 3.
Figure 3.
ELISA assay of plasma CFD concentration in AMD and control subjects in the combined UK 1 and UK 2 series. The difference was statistically significant both in the combined sexes (P = 0.00025; upper panel) and in females (P = 0.0004) but not in males.
See this image and copyright information in PMC

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