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Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.

Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.

Authors :
Zouache, M. A.
Richards, B. T.
Pappas, C. M.
Anstadt, R. A.
Liu, J.
Corsetti, T.
Matthews, S.
Seager, N. A.
Schmitz-Valckenberg, S.
Fleckenstein, M.
Hubbard, W. C.
Thomas, J.
Hageman, J. L.
Williams, B. L.
Hageman, G. S.
Source :
Nature Communications; 1/10/2024, Vol. 15 Issue 1, p1-17, 17p
Publication Year :
2024

Abstract

Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch's membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD. Complement factor H-related 4 protein (FHR-4) has been implicated in the pathophysiology of age-related macular degeneration (AMD). Here, in contrast, the authors find that levels of FHR-4 in plasma or ocular tissue do not appear to influence susceptibility to AMD or its course of progression, questioning whether modulation of FHR-4 is likely to be an effective therapeutic strategy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
174711284
Full Text :
https://doi.org/10.1038/s41467-023-44605-0