CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).
CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).
A sensitivity analysis of genetic variants known to be associated with late stage AMD showed that rs1061170 (p.Y402H) in the complement factor H (CFH) gene influences the association of Cer d18:1/16:0 with GA. To understand the possible influence of this genetic variant on ceramide levels, we established a cell-based assay to test the modulation of genes in the ceramide metabolism by factor H-like protein 1 (FHL-1), an alternative splicing variant of CFH that also harbors the 402 residue.
A statistically significant difference in allele frequencies between dt-GA and ndt-GA were found for CFH:rs1061170 and CFH:rs800292 (Pcorrected = 0.03).
Patients with GA were significantly older, with a higher prevalence of reticular pseudodrusen, bilateral involvement of advanced AMD and T-allele frequency of ARMS2A69S compared with those with typical AMD and PCV; although there were no differences in the genetic and clinical characteristics among patients with GA and RAP.
Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71).
Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71).
Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2_rs10490924 [P < 0.00088] and C3_rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]).
In fact, we demonstrate that gene variants of CFH and CFB, as well as demographic risk factors, confer significant risk for GA progression (both rate of progression and relative growth) within a Spanish population.
Early AMD lesion characteristics were assessed for association with GA incidence using eye-specific data and generalized estimating equation models adjusting for age, current smoking, and presence of risk alleles of the complement factor H (CFH) or age-related maculopathy susceptibility 2 (ARMS2) genes, genotyped or imputed using genome-wide scan data.
Early AMD lesion characteristics were assessed for association with GA incidence using eye-specific data and generalized estimating equation models adjusting for age, current smoking, and presence of risk alleles of the complement factor H (CFH) or age-related maculopathy susceptibility 2 (ARMS2) genes, genotyped or imputed using genome-wide scan data.
Although genetic markers were associated significantly with 3-year CNV (CFH: Y402H; ARMS2: A69S) and GA incidence (CFH: Y402H), the inclusion of genetic factors in the models provided only marginal improvements in predictive performance.
In this series, in patients with geographic atrophy or choroidal neovascularization in at least 1 eye, the ARMS2A69S substitution strongly associated with geographic atrophy or choroidal neovascularization in the fellow eye.
Although genetic markers were associated significantly with 3-year CNV (CFH: Y402H; ARMS2: A69S) and GA incidence (CFH: Y402H), the inclusion of genetic factors in the models provided only marginal improvements in predictive performance.
The frequency of the T allele of ARMS2/HTRA1 rs10490924 was significantly higher in participants with CNV than in those with geographic atrophy (OR, 1.37; 95% confidence interval, 1.21-1.54; P value = 4.2 × 10(-7)).
CFH confers more risk to the bilaterality of geographic atrophy, whereas HTRA1/LOC387715 contributes more to the bilaterality of choroidal neovascularization.