International research has shed light on the role that two genes – Complement Factor H (CFH) and Factor H-Related 1 to 5 (FHR1-5) – play in the development of age-related macular degeneration (AMD).1
For many years, we have known that inflammation at the back of the eye plays a role in AMD development. Genetics studies have identified a series of genes which regulate the activity of the complement pathway – a key player in our immune defence against pathogens – that affect a person’s risk of developing the disease. The suggestion from these data is that AMD is caused, at least in part, by a failure of complement regulation in the eye. However, until now the role of these genes – CFH and FHR1-5 – has been unclear.
By using mass spectrometry, scientists studied the levels of the CFH and FHR1-5 in the blood, and were able to show, for the first time, that all five FHR proteins are at higher levels in people with AMD than in those without. This builds on published research that found FHR4 was higher in individuals with AMD2 and that FHR1 and FHR2 seem to have the largest increase.
The team also studied the genes which code for these proteins, and confirmed that the genes modify the risk of AMD which are controlling these levels. This strongly suggests increases in these blood proteins, driven by the genetic risk, can modify activity of the complement pathway and drive AMD development.
- Beyond factor H: The impact of genetic-risk variants for age-relate macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations DOI: https://doi.org/10.1016/j.ajhg.2021.05.015
- Cipriani, V., Lorés-Motta, L., He, F. et al. Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration. Nat Commun 11, 778 (2020). https://doi.org/10.1038/s41467-020-14499-3