Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.
Nat Commun
; 15(1): 443, 2024 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-38200010
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator H do Complemento
/
Degeneração Macular
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article