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P. N. Baird, A. F. M. Islam, A. J. Richardson, R. H. Guymer; A Tag SNP Approach Defines a Minimal Risk Associated Region in the CFH Gene in Individuals With AMD. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1267.
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The complement factor H (CFH) gene represents one of the major genes associated with age related macular degeneration (AMD). Although a number of variants and haplotypes have been described across the CFH gene a specific region that could explain the majority of its association with AMD has not been fully explored.
Nine single nucleotide polymorphisms (SNP) were used to tag the CFH gene. These tagSNPs were selected based on available HapMap data. An additional 10 SNPs previously described as significantly associated with AMD or previously described in haplotypes by Hageman et al (2005) were also genotyped. Patients and controls (no AMD) were recruited from Melbourne, Victoria as per Declaration of Helsinki guidelines. Allelic and genotype frequencies together with odds ratios were calculated. Logistic regression to identify dominant SNPs and haplotype analysis using haploview was also undertaken.
A total of 196 AMD cases and 126 controls (no AMD) were genotyped. The 2 tagSNPs rs1329421 and rs393955 each presented with the greatest association with AMD (p=4x10-13 and p=8x10-13 respectively). However, following conditional analysis only the tagSNP rs393955 remained as the major SNP showing independence from other tagSNPs. CFH haplotypes constructed using these 2 tagSNPs appeared to explain the majority of the association for CFH (p=1.96x10-13) as their association was similar to that for haplotypes derived from the entire CFH gene (1.28x10-13) and to haplotypes previously described by Hageman et al (2.4x10-13). Inclusion of the additional SNPs rs1061170 (Y402H) and rs2274200 identified a strongly associated region (1.98x10-15) of the CFH gene as a 33kb region stretching from rs1061170 (Y402H) to rs393955.
A small 33kb region of the CFH gene defines the site of maximal association with AMD. Development of future therapeutic interventions would therefore be best focussed on this region.ReferenceHageman GS et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA. 2005;102:7227-7232, 2005
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