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.
Collectively, we demonstrated that the complement factor B genes rs641153 and rs4151667, but not rs1048709, rs2072633, rs12614, were associated with the susceptibility of age-related macular degeneration and might play predictive roles in future age-related macular degeneration diagnosis.
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.
In this post hoc analysis of cross-sectional data from US participants in the Comparison of AMD Treatments Trials, genotyping was performed in 835 participants with TaqMan assays for the SNPs rs1061170 (Y402H variant in CFH), rs800292 (rs800292" genes_norm="3075">I62V variant in CFH), rs10490924 (rs10490924;s10490924" genes_norm="387715;717">A69S variant in ARMS2), rs11200638 (HTRA1), rs547154 (C2), rs2230199 (rs2230199" genes_norm="5654;718">R102G variant in C3), rs10468017 (LIPC), and rs4151667 (L9H variant in CFB).
Using a panel of 8854 SNPs associated with AAMD at p-values ≤5.0E-7 from a cohort of >30,000 elderly people, we identified SNPs in miRNA target-encoding constituents of: (1) regulator of complement activation (RCA) genes (rs390679, CFHR1, p≤2.14E-214 ; rs12140421, CFHR3, p≤4.63E-29); (2) genes of major histocompatibility complex (MHC) loci (rs4151672, CFB, p≤8.91E-41 ; rs115404146, HLA-C, p≤6.32E-12 ; rs1055821, HLA-B, p≤1.93E-9 ; rs1063355, HLA-DQB1, p≤6.82E-14); and (3) genes of the 10q26 AAMD locus (rs1045216, PLEKHA1, p≤4.17E-142 ; rs2672603, ARMS2, p≤7.14E-46).
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)).
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.
Haplotype and conditional analysis of the C2-CFB-SKIV2L locus showed a low-frequency variant (R74H) in CFB would be individually associated with AMD susceptibility independent of the GWAS associated SNP.
To elucidate whether polymorphisms of C2, C3, and CFB genes are major genetic determinants of age-related macular degeneration (AMD) in a Greek population.
The CFB (R32Q) polymorphism was associated with AMD characterized by small drusen only, and appeared to be protective of large drusen (OR 0.48/0.45) and of larger drusen covered area (OR 0.34).
The associations between genetic variants located in CFH, CFB, ARMS2 and HTRA1 and the risk of age-related macular degeneration (AMD) in a northern Chinese population were investigated.
An association analysis was performed of the C2-CFB-RDBP-SKIV2L locus with both neovascular AMD and PCV in a Chinese population using 19 haplotype-tagging single nucleotide polymorphisms (SNPs) and 6 previously reported SNPs across the C2-CFB-RDBP-SKIV2L region.
Seventeen single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes including CFH (rs800292, rs3766404, rs1061170, rs2274700 and rs393955), HTRA1 (rs11200638), CFHR1-5 (rs10922153, rs16840639, rs6667243, and rs1853883), LOC387715/ARMS2 (rs3793917 and rs10490924), C3 (rs2230199 and rs1047286), C2 (rs547154), CFB (rs641153) and F13B (rs6003) were examined.
PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3.
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.