Local and not systemic factor H production dictates risk of age-related macular degeneration in liver transplant recipients

Sam Khandhadia, Svetlana Hakobyan, Ling Z. Heng, Jane Gibson, David H. Adams, Graeme J. Alexander, Jonathan M. Gibson, Keith Martin, Geeta Menon, Kathryn Nash, Sobha Sivaprasad, Sarah Ennis, Angela J. Cree, Paul Morgan, Andrew J. Lotery

Research output: Contribution to journalConference abstractpeer-review


Age-related macular degeneration (AMD) is the commonest cause of blindness in the developed world, and is strongly associated with the Y402H polymorphism in the complement (C) factor H (CFH) gene. As liver is the primary site of C production, our hypothesis was that modification of liver CFH Y402H genotype through liver transplantation would influence the development of AMD. We recruited 223 Western European patients at least 55 years old, who had undergone LT at least 5 years previously. 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 by previously described ELISA utilising variant-specific monoclonal antibodies. This approach was verified by genotyping donor tissue from a subgroup of patients (n = 49). We found that recipient AMD status was associated with recipient CFH Y402H genotype (p = 0.036) but not with donor CFH Y402H genotype (p = 0.626), after controlling for age, gender, smoking status, and body mass index. Compared to previously reported prevalence figures there was an increased prevalence of both AMD and recipient CFH Y402H risk allele frequency in LT patients. Plasma C protein levels (including C3 and C4, activation products C3a, C4a, C5a, TCC, and regulators C1 inhibitor and CFH) were similar in LT patients with and without AMD. We also compared LT patients with 30 randomly selected age matched healthy controls, without AMD or a history of LT. Plasma total CFH was higher in LT patients compared to controls, otherwise levels of all other C proteins were similar. AMD was associated with recipient CFH Y402H genotype, implying that local rather than systemic CFH protein or gene therapy may be more relevant for pathogenesis and a better target for therapy in AMD. The increased prevalence of AMD in LT patients may be explained by the observed increased frequency of the CFH 402H sequence variant
Original languageEnglish
Article number152
Pages (from-to)1182-1183
Number of pages2
Issue number11
Publication statusPublished - 1 Nov 2012
EventXXIV International Complement Workshop - Minoa Palace Conference Center, Chania, Crete, Greece
Duration: 10 Oct 201215 Oct 2012


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