Complement Genes Play Role in Age-Related Macular Degeneration

MedicalResearch.com Interview with:

dr-anneke-i-den-hollanderAnneke I. den Hollander, PhD
Department of Ophthalmology and Department of Human Genetics
Donders Institute for Brain, Cognition, and Behaviour
Radboud University Medical Center
Nijmegen, the Netherland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Age-related macular degeneration is caused by a combination of genetic and environmental factors. Rare genetic variants in the complement system have been described in AMD, but their effect remains largely unexplored. In this study we aimed to determine the effect of rare genetic variants in the complement system on complement levels and activity in serum.

MedicalResearch.com: What are the main findings?

Response: Carriers of CFI variants showed decreased FI levels, carriers of C9 Pro167Ser had increased C9 levels, while C3 and FH levels were not altered. Carriers of CFH and CFI variants had a reduced ability to degrade C3b, which for CFI was linked to reduced serum FI levels.

MedicalResearch.com: What should readers take away from your report?

Response: Carriers of rare variants in CFI and CFH are less able to inhibit complement activation and may benefit more from complement inhibiting therapy than AMD patients in general.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Several clinical trials are currently evaluating complement inhibiting treatments in  age-related macular degeneration. Selection of patients with high levels of complement activation would lead to more effective clinical trials, requiring smaller patient groups to demonstrate an effect of the drug being tested. Screening of individuals for genetic (e.g. rare variants in CFH and CFI) or serum (e.g. reduced FI levels) biomarkers will enable treatment in an early phase of the disease, before substantial tissue damage has occurred. Personalized treatment could be provided for patients with rare genetic variants in the CFH and CFI genes or reduced FI levels, linked to the functional inability to degrade C3b efficiently, and act on this effect by using complement inhibitors.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Geerlings MJ, Kremlitzka M, Bakker B, Nilsson SC, Saksens NT, Lechanteur YT, Pauper M, Corominas J, Fauser S, Hoyng CB, Blom AM, de Jong EK, den Hollander AI. The Functional Effect of Rare Variants in Complement Genes on C3b Degradation in Patients With Age-Related Macular Degeneration. JAMA Ophthalmol. Published online December 01, 2016. doi:10.1001/jamaophthalmol.2016.4604

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Last Updated on December 12, 2016 by Marie Benz MD FAAD