Genetic Association of Known Risk Alleles With Different Lesion Types in Age-Related Macular Degeneration

Abstract

Purpose: : The course of visual acuity as well as the response to anti-VEGF treatment of exudative age-related macular degeneration differs among lesion types. In order to improve rationales for treatment strategies, we assessed genetic polymorphisms of known AMD susceptibility loci and compared the observed different allele frequencies among patients showing different lesion types.

Methods: : Eyes that were treated with Ranibizumab during the time course of at least 12 months were analyzed. Genotypes for five SNPs, which previously had been shown to be involved in AMD, were determined by DNA sequencing or the Taq-man SNP assay. We investigated the prevalence and distribution of the different genetic polymorphism among eyes that were classified as having predominantly classic, minimally classic or occult lesions. Statistical calculations of odds ratio are only shown when statistically significant (Chi square >3.84; p< 0.05).

Results: : Assessment of all AMD patients showed association of rs1061170 (CFH) (odds ratio of 1.9). Similarly, patients with minimally classic and occult lesion types showed association of comparable strength. In contrast, the effect increased (odds ratio of 2.5) for patients with predominantly classic lesion types. Comparable results were obtained for rs11200638 (HTRA1). SNP rs10490924 (LOC387715) showed association for all patients with an odds ratio of 2.5 which increased to 2.9 for patients with occult lesion type.

Conclusions: : Our results show early indications for the assumption that a different genetic imprint underlies the established angiographic classification. These observations could not only help explain some of the differences in the natural courses of the diseases, but could further have a significant meaning for future prevention and therapy strategies.

Keywords: age-related macular degeneration • genetics • choroid: neovascularization