Table 1 Genes associated with GA/AMD
Gene | Protein | Activity | Impact of mutation/polymorphism on protein product function | Mutation impact on complement activity | GA risk |
|---|---|---|---|---|---|
CFH | Factor H (FH) | Cofactor for FI-mediated cleavage of C3b; Competes C1q binding; Competes FHR1 | Decrease surface binding of FH decreases FI cleavage; allows C1q binding | Increase | Increase OR = 2.7–7.4 |
CFHR1/3 | FHR1 and / or FHR3 | Stabilizers C3b; enhances C1q binding; Competes FH | Gentic deletion allows more FH binding, greater FI cleavage of C3b, less C1q binding | Decrease | Decrease OR = 0.35 |
CFI | Factor I (FI) | Cleaves C3b to inhibit cascade activity and to produce Ic3b for opsonization/phagocytosis | Reduced FI levels / activity | Increase | Increase OR up to 22 |
C2 | C2 | Drives classical / lectin activation of C3 | Uncharacterized | Increase | Decrease OR = 0.47–0.49 |
CFB | Factor B (FB) | Drives alternative / AP amplification via activation of C3 | Decrease activity | Decrease | Decrease OR = 0.41–0.54 |
C3 | C3 | Activation leads to C3b as opsonin and plateform for AP amplification or C5 cleavage | Resistance to inactivation by FI cleavage | Increase | Increase OR 2.8 |
C9 | C9 | Component of membrane attack complex(MAC) | Increased MAC polymerization | Increase | Increase OR 2.2 |