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Age-related macular degeneration and modification of systemic complement factor H production through liver transplantation

Khandhadia, Samir, Hakobyan, Svetlana, Heng, Ling Z., Gibson, Jane, Adams, David H., Alexander, Graeme J., Gibson, Jonathan M., Martin, Keith R., Menon, Geeta, Nash, Kathryn, Sivaprasad, Sobha, Ennis, Sarah, Cree, Angela J., Morgan, Bryan Paul and Lotery, Andrew J. 2013. Age-related macular degeneration and modification of systemic complement factor H production through liver transplantation. Ophthalmology 120 (8) , pp. 1612-1618. 10.1016/j.ophtha.2013.01.004

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Abstract

Purpose To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD). Design Multicenter, cross-sectional study. Participants We recruited 223 Western European patients ≥55 years old who had undergone LT ≥5 years previously. Methods We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor). Main Outcome Measures We evaluated AMD status and recipient and donor CFH Y402H genotype. Results In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0–2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014). Conclusions Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0161-6420
Last Modified: 20 Apr 2019 23:32
URI: http://orca-mwe.cf.ac.uk/id/eprint/75674

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