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DNA profile strongly associated with exudative age‐related macular degeneration
Author(s) -
CARTER JG,
ARISTODEMOU P,
CHERRY J,
CHURCHILL AJ
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.6354.x
Subject(s) - factor h , linkage disequilibrium , single nucleotide polymorphism , macular degeneration , genotype , snp , biology , vascular endothelial growth factor , genetics , medicine , gene , vegf receptors , ophthalmology , antibody , complement system
Purpose The genetics of age‐related macular degeneration (AMD) is slowly unfolding with the recent discovery that single nucleotide polymorphisms (SNPs) in 4 genes, Complement Factor H (CFH), ARMS2/LOC387715, HTRA1 and Vascular endothelial growth factor (VEGF) independently confer a greater risk of disease. We have taken this further and analyzed a combined DNA profile for the SNPs in these 4 genes. Methods Patients with exudative AMD (n=45) and age‐matched controls (n=94) were genotyped for the CFH Y402H (rs1061170), ARMS2 A69S (rs10490924), HTRA1 ‐512 (rs11200638), and the VEGF +674 (rs1413711) polymorphisms, by RFLP, AS‐PCR and randomized sequencing. Statistical analysis was carried out for each individual loci and into a combined DNA profile using the PHASE program. Results Association of the VEGF +674CC genotype with AMD has been previously reported. We observed strong associations with AMD and the CFH‐CC [OR=11.9 (4.5,31.3), p=0.184], ARMS2‐TT [OR=4.7 (1.6, 13.8), p=0.0023] and HTRA1‐AA [OR=3.6 (1.3,10.1), p=0.0128] genotypes respectively. We also observed strong linkage disequilibrium between rs10490924 and rs11200638 (r2=0.9138), as seen in previous studies. However, possession of the 4 SNP DNA profile: CTAC (CFH/ARMS2/HTRA1/VEGF) is strongly associated with AMD [OR=63.0 (8.3, 475.4), p<0.00001]. Conclusion Past associations between CFH, ARMS2 & HTRA1 have already been reported, and this data further supports this. However, the possession of the CTAC ‘at risk’ DNA profile shows the potential combined effects of these three genes, and their strong association with AMD. It is now possible to identify those most at risk in the general population allowing lifestyle choices to be made that could reduce the overall risk of AMD.