There were no differences between the major AMD risk single-nucleotide polymorphisms (SNPs) of the CFH, HTRA1 or C3 genes, expect for somewhat longer telomeres in controls with the C3 risk SNP.
The CFHY402H genotype CC was associated, relative to genotype TT (reported as hazard ratio; 95% CI), with increased incidence of AMD (no to minimally severe early AMD, 1.98; 1.57-2.49), progression of AMD (minimally severe early to moderately severe early AMD, 1.73; 1.29-2.33; moderately severe early to severe early AMD, 1.30; 0.86-1.94; and severe early to late AMD, 1.72; 1.01-2.91) but not with regression of AMD or mortality.
The haplotype tagging Y402H polymorphism in the Complement Factor H gene (CFH) has consistently been associated with age-related macular degeneration, whereas conflicting results have been reported on its relationship with cardiovascular disease.
We confirmed the association of age-related maculopathy susceptibility 2 (ARMS2) rs10490924 (P=7.38 × 10<sup>-17</sup>), HTRA1 rs11200638 (P=5.47 × 10<sup>-17</sup>) and complement factor H gene (CFH) rs800292 (P=2.53 × 10<sup>-8</sup>) with neovascular AMD, all loci passing the genome-wide significance level (P<5.22 × 10<sup>-8</sup>).
DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant, Y402H, that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57.
Our study demonstrated that the presence of the Y402H polymorphism in complement factor H is significantly associated with increased susceptibility to early AMD in Taiwan Chinese populations and that the C allele frequency is low in these populations.
Age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and membranoproliferative glomerulonephritis type II (MPGN2) are associated with polymorphisms or mutations in the FH gene (Cfh), suggesting the existence of a genotype-phenotype relationship.
A significant interaction between the CETP SNP rs3764261 and the CFH SNP rs800292 existed in both neovascular AMD and PCV, the rs800292 G allele conferring a significantly increased risk of the diseases only in individuals carrying the risk allele T of rs3764261.
Mutations and SNPs (single nucleotide polymorphisms) in Factor H have been implicated in a variety of human conditions including age-related macular degeneration (AMD), atypical hemolytic uremic syndrome, and membranoproliferative glomuleronephritis type II or dense deposit disease.
However, the association with the CFHY402H risk allele appeared to be stronger, whereas the association with smoking was less pronounced when compared to AMD as a whole.
Two protective, low-frequency, non-synonymous variants were significantly associated with a decrease in AMD risk: A307V in PELI3 (odds ratio [OR] = 0.14, P = 4.3 × 10-10) and N1050Y in CFH (OR = 0.76, P = 6.2 × 10-12).
Total fH concentration was similar in each subgroup of young and elderly control subjects; however, in the AMD group, fH concentration was significantly higher in the heterozygous subgroup.
Association of risk genotypes of ARMS2/LOC387715 A69S and CFHY402H with age-related macular degeneration with and without reticular pseudodrusen: a meta-analysis.
To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes.
This meta-analysis summarizes the strong evidence for an association between CFH and AMD and indicates a multiplicative model with each C allele increasing the odds of AMD by approximately 2.5-fold.