The T allele of rs10033900, which is located 2781 bp upstream of the 3′ untranslated region of the complement factor I gene (
CFI), has been associated with increased risk of exudative AMD in Caucasians.
44,47 Both complement factors I and H are complement regulatory proteins.
CFH encodes factor H, the most important alternative pathway discriminator that binds C3b and prevents the formation of C3 convertase and acts as a cofactor of factor I to cleave C3b in iC3b.
49 CFI is expressed by hepatocytes, macrophages, lymphocytes, endothelial cells, and fibroblasts and encodes factor I, a regulator protein of the three complement pathways.
50 By cleaving of C3b and C4b, factor I reduces the formation of the C3 and C5 convertase enzymes.
50 Other genes in the complement cascade pathway are associated with exudative AMD, including
CFH, C2, CFB, and
C3.
34–36,39–43 Interestingly,
CFH (rs1061170,
P = 0.04) and
CFI (rs10033900,
P = 0.0023) appeared to be related to myopic CNV in this study after adjustment for age, sex, and degree of myopia, and
CFI remained significant after adjustment for multiple testing. The possible difference in effect of
CFI compared with
CFH on myopic CNV risk may be related to the fact that factor I is involved in the classic, lectin and alternative pathways, while factor H is only involved in the regulation of the alternative pathway.
55 It is interesting to note that the gene on chromosome 10,
ARMS2/HTRA1, was not related to myopic CNV in this study even though this gene is more strongly associated with CNV compared with geographic atrophy in AMD
47,56 and also more strongly associated with all AMD subtypes when compared with the CFH at-risk common variant.
57 It is also noteworthy that the SNPs in the VEGF gene were not related to myopic CNV, given that
VEGF rs4711751 is related to advanced dry and exudative AMD.
47