1093 patients with exudative AMD and 396 controls have been recruited and genotyped for the Y402H of CFH, rs10490924 of ARMS2 and T280M of the CX3CR1 gene.
Age-related macular degeneration (AMD), a complex multigenic disorder and the most common cause of vision loss in the elderly, is associated with polymorphisms in the LOC387715/ARMS2 and HTRA1 genes on 10q26.
ARMS2 was mainly distributed in the cytosol, not in the mitochondrial outer membrane as previously reported, suggesting that ARMS2 may not confer risk to AMD through the mitochondrial pathway.
ARMS2rs10490924 was also significantly associated with the risk allele T found at a frequency of 0.5 in AMD and 0.15 in controls (p < 0.017, χ(2) test).
Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala(69)→Ser, did not improve the statistical model.
After adjusting for age, gender, ARMS2A69S, and CFHI62V, the A allele of rs429608 was significantly protective against neovascular AMD (odds ratio [OR] 0.24, 95% confidence interval [CI] 0.122-0.484, p < 0.001), PCV (OR 0.43, 95% CI 0.262-0.704, p = 0.001), RAP (OR 0.09, 95% CI 0.014-0.581, p = 0.011).
After adjusting for age, sex, body mass index, smoking status, age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) genotypes, and other factors, mean IMT was associated with the 10-year incidence of early AMD (odds ratio [OR] per 0.1 mm IMT, 1.11; 95% confidence interval [CI], 1.00-1.21; P = 0.03) and late AMD (OR per 0.1 mm IMT, 1.27; CI, 1.10-1.47; P = 0.001).
After multivariate adjustment, CFH Y402H and ARMS2A69S polymorphisms were associated with very high risk for exudative AMD (OR = 6.21 and OR = 11.7, respectively, p < 0.0001).
After ranibizumab treatment, AMD patients without risk alleles in the CFH and ARMS2 genes (4.8%) demonstrated a mean VA improvement of 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, whereas no VA improvement was observed in AMD patients with 4 CFH and ARMS2 risk alleles (6.9%; P = 0.014).
Age and the T allele of ARMS2A69S are the risk factors requiring retreatments, leading to poor visual change in eyes with exudative AMD following the initial 3-monthly IVR.
Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample.
Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown.
Among different genotype combinations ARMS2-CFH and CFH-C3 combinations have the most significant levels of synergism and C3-CFI combination has the most significant level of antagonism in AMD patients.