gms | German Medical Science

7th International Symposium on AMD: Age-related Macular Degeneration – Understanding Pathogenetic Mechanisms of Disease

20.09. - 21.09.2019, Baden-Baden

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Rare genetic variants in geographic atrophy

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  • Andrew Lotery - University of Southampton/GB
  • J R. Sutton - University of Southampton/GB
  • S. Khandhadia - University Hospital Southampton/GB
  • G. Menon - Frimley Health NHS Foundation Trust, Camberley/GB
  • C. Bailey - University of Bristol/GB
  • S. Sivasprasad - University City London/GB
  • Q. Mohamed - Gloucestershire Hospitals NHS Foundation Trust, Cheltenham/GB
  • P. Bishop - University of Manchester/GB
  • P. Charbel Issa - University of Oxford/GB
  • D. Steel - City Hospital Sunderland NHS Foundation Trust, Sunderland/GB
  • T. Peto - University Hospitals Bristol NHS Foundation Trust, Bristol/GB
  • W. Amoaku - University Hospitals NHS Trust, Nottingham/GB
  • R. Arora - NHS Foundation Trust, Salisbury/GB
  • P. Prakash - Princess Alexandra Hospital NHS Trust, Harlow/GB
  • W. Innes - Eye Centre, Newcastle/GB
  • R. Maclaren - University of Oxford/GB
  • D. Kavanagh - University of Newcastle/GB

7th International Symposium on AMD: Age-related Macular Degeneration - Understanding Pathogenetic Mechanisms of Disease. Baden-Baden, 20.-21.09.2019. Düsseldorf: German Medical Science GMS Publishing House; 2020. Doc19amd10

doi: 10.3205/19amd10, urn:nbn:de:0183-19amd108

Veröffentlicht: 5. Februar 2020

© 2020 Lotery et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

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Background: Rare variants in complement factor I (CFI) are strongly associated with risk of developing AMD (Age-related Macular Degeneration). Furthermore low systemic CFI levels have been found in patients with AMD. We aimed to identify the prevalence of patients with advanced dry AMD (geographic atrophy) who also had low systemic CFI protein levels and CFI genetics mutations. Our hypothesis is these patients may benefit from Complement Factor I supplementation.

Methods: 13 hospitals in the United Kingdom invited patients with geographic atrophy to participate in this ethically approved study. Patients had serum Complement Factor I and C-reactive protein measured. If serum CFI levels were low, sequencing of CFI was undertaken to identify rare variants. CFI levels were measured by ELISA and genetic analysis was undertaken using Sanger sequencing and performed by Multiplex Ligation-dependent Probe Amplification.

Results: Currently 409 patients have been recruited. Of these 66 patients have a low serum CFI level defined as below 15.6 ug/mL ie 16 %. Range of CFI proteins (6.2 - 36.0 ug/mL). Of those patients with a low CFI serum level, 9 had an identified rare variant in CFI and 57 did not (2% 0f the total population). In patients with a low CFI level C-RP range and average was <0.3 – 14.2mg/L (2.09) and for those with a normal CFI level, 0.4 – 59 mg/L (4.62) The range and average age of GA patients with CFI mutations was 61-84 with (77) and of those without 46 – 101 (79).

Conclusions: In the UK rare variants in CFI with low serum levels are found in 2 % of patients with geographic atrophy. These patients might be particularly suitable for CFI supplementation in future therapeutic trials.