We investigated two SNPs in C2 and two in CFB in independent case-control and family cohorts of white subjects and found rs547154, an intronic SNP in C2, to be significantly associated with ARM in both our case-control (P-value 0.00007) and family data (P-value 0.00001).
Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia: Another mechanism of complement activation in age-related macular degeneration.
The CFB variant 32W was associated with protection against neovascular AMD, compared to the common 32R variant (odds ratio 0.64, p<0.05, in logistic regression with CFB variants; odds ratio 0.53, p<0.05, in logistic regression with CFB variants, CFH haplotypes, HTRA1 rs10490924 genotype, and smoking status).
The CD subtype of AMD was significantly associated with current smoking as well as variants in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), complement factor B/complement component 2 (CFB/C2), complement component 3 (C3), and apolipoprotein E (APOE) genes.
Several variants in the complement cascade genes (complement factor H [CFH], C2, C3, CFB, and Serping1) have been reported to associate with age-related macular degeneration (AMD).
To elucidate whether polymorphisms of C2, C3, and CFB genes are major genetic determinants of age-related macular degeneration (AMD) in a Greek population.
Here we describe a novel complotype composed of CFB (rs4151667)-CFB (rs641153)-CFH (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10(-13)) and complement activation levels in vivo (p = 8.31*10(-9)).
We performed an association analysis between PCV and polymorphisms across the C2-CFB-RDBP-SKIV2L region in a Japanese population, genotyping 13 single nucleotide polymorphisms (SNPs) spanning this region, including rs9332739 (E318D), rs547154, rs4151667 (L9H), and rs641153 (rs641153" genes_norm="629">R32Q) that are known to be associated with age-related macular degeneration (AMD).
Studies that investigated associations between C2 (rs547154 and rs9332739), C3 (rs1047286), CFB (rs4151667 and rs641153), and CFH (rs551397 and rs2274700) polymorphisms and AMD were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Library databases for articles published prior to January 1, 2018.
Furthermore, this association is independent of known AMD-associated risk variants in the nearby CFB/C2 locus, particularly in females and in individuals over 78 years.
A significant genotype and variant allele association was found of rs10490924 in ARMS2/HTRA1 with wet AMD, while the SNPs in CFH, CFB, and C3 were not associated with AMD in the current Pakistani cohort.