Susceptibility genes and progression in age-related maculopathy: a study of single eyes

The specific role of single-nucleotide polymorphisms (SNPs) in the progression of age-related maculopathy (AMD) is not clearly understood. The present study was conducted to investigated whether variants in three susceptibility genes are differentially associated with progression to early and late AMD.

The Münster Ageing and Retina Study (MARS) cohort includes 722 patients with different stages of AMD. Participants were reexamined after a median of 2.6 years. The association of SNPs in the CFH, ARMS2, and C3 genes with AMD progression was evaluated in 1435 single eyes by using multivariate logistic regression models with generalized estimating equations.

CFH-rs1061170 was significantly related to the development of early (OR = 1.94, 95% confidence interval [CI], 1.3-3.0 for heterozygous, and OR = 2.9 [95% CI, 1.7-5.1] for homozygous allele carriers) but not to late AMD. In contrast, ARMS2-rs10490924 was associated only with progression to advanced disease (OR = 1.2 [0.7-2.1] and OR = 2.1 [1.1-3.9], respectively). The variant C3-rs2230199 showed no relation with AMD progression.

The findings indicate that AMD progression is differentially affected by genotypic variants. Probably, aging processes of the human retina predispose to AMD onset in the presence of genetic variation in the complement system, which alters immunoregulatory and inflammatory responses. The specific functional role of ARMS2-rs10490924 remains as yet unknown, but it appears to mainly affect the progression to late AMD stages.