ERCC6 C-6530>G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD.
In a case-control study drawn from a US-based population of European descent, we have identified a previously unrecognized common, noncoding variant in CFH, the gene encoding complement factor H, that substantially increases the influence of this locus on AMD, and we have strongly replicated the associations of four other previously reported common alleles in three genes (P values ranging from 10(-6) to 10(-70)).
We detected a strong association between the C/C-genotype compared to the T/T-genotype of Tyr402His polymorphism (first base of the Tyr-codon changes) of the CFH gene and AMD in the AMD cases compared to the non-AMD (p=8.86x10(-12)) or to blood donor controls (p=2.02x10(-13)).
We conducted a case-control association study to investigate the association of 6 single nucleotide polymorphisms (SNPs) in CFH with exudative AMD in the Chinese population.
A prospective assessment of the Y402H variant in complement factor H, genetic variants in C-reactive protein, and risk of age-related macular degeneration.
Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.
CFH and LOC387715/HTRA1 haplotypes and smoking status exerted large effects on AMD susceptibility, enabling risk scores to be generated with appropriate weighting of these three factors.
In addition, we identify the Factor H-like protein 1 (FHL-1), an alternative splice product of the CFH gene as an additional protein that includes the risk residue 402, and thus confers risk for AMD.
On the basis of this and other results it is tempting to speculate that the combined effect of variants in the CFH and LOC 387715 genes may contribute to the AMD phenotype in this family.
We utilized a population-based case-control study design of early AMD among Latinos/Hispanics to evaluate the CFHTyr402His polymorphism for an association with early AMD phenotypes.
The CFHY402H and LOC387115 A69S polymorphisms were each independently related to progression from early or intermediate stages to advanced stages of AMD, controlling for demographic factors, smoking, body mass index, and AREDS vitamin-mineral treatment assignment, with odds ratios (ORs) of 2.6 (95% confidence interval [CI], 1.7-3.9) for CFH and 4.1 (95% CI, 2.7-6.3) for LOC387715 for the homozygous risk genotypes (P<.001 for trend for each additional risk allele for both genes).
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.
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.
The discovery of strong associations of the His402 variant of complement factor H (CFH) and the change in the promoter region of HtrA serine peptidase 1 (HTRA1) with age-related macular degeneration (AMD) have altered our conception of the pathophysiology of this disease.
The present study was undertaken to investigate whether four coding and noncoding variants of the CFH gene, including rs1410996, are associated with AMD in native, unrelated Japanese patients.