Influence of CFH, HTRA1 and ARMS2 haplotype polymorphisms in the development of age-related macular disease.

OBJECTIVE To demonstrate genetic influence on the onset of age-related macular disease (AMD), analyzing genotype distribution of haplotypes, including polymorphisms of genes with proved relationships with AMD risk (CFH, ARMS2, HTRA1) in patients with AMD and in healthy people. METHODS We took 101 consecutive patients with an AMD diagnosis following Wisconsin international classification. For our control group, we took 91 patients without AMD or any significant macular changes. We analyzed CFH rs1410996, ARMS2rs 10940923 polymorphisms using real time PCR with taqman probes, and HTRA1 -625 using restriction endonuclease digestion. We studied haplotypes by simultaneously combining genotypes which, in previous studies, had been shown to have relationship with AMD (CFH, ARMS2, HTRA1) in patients with AMD and healthy people. RESULTS There was a statistically significant higher proportion of patients with AMD simultaneously expressing CFH GG (rs1410996) and ARMS2 TT (rs10940923) (P=.037; OR: 7.742 [1.010-63.156]); ARMS2 TT (rs10940923) and HTRA1-625 TT (P=.001; OR: 9.006 [2.019-40.168]) and CFH GG (rs1410996), ARMS2 TT (rs1040923) and HTRA1 -625 GG (P=.043; OR: 6.702 [1.003-55.565]) genotypes. CONCLUSIONS Haplotypes which combine "risk genotypes", demonstrated in previous studies, of our analyzed polymorphisms are more frequent in patients with AMD than in the control group, and they seem to increase the risk of suffering the disease in our population.