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.
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.
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.
To assess the associations between the CFH gene and AMD in the general population and to investigate the modifying effect of smoking, serum inflammatory markers, and genetic variation of C-reactive protein (CRP).
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.
This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups.
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.
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)).
Significant association (P = 4.95 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.
Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.
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.