Phenotype analysis of patients with the risk variant LOC387715 (A69S) in age-related macular degeneration.

PURPOSE: To examine phenotypes of age-related macular degeneration (AMD) patients with the LOC387715 variant (T allele at rs10490924, A69S). DESIGN: Retrospective, observational case series. METHODS: This clinic-based case series data set contained 775 unrelated cases of AMD. AMD phenotypes of three groups, determined by the number of LOC387715 risk alleles, were compared regarding the presence or absence of 16 phenotypic features. RESULTS: The number of AMD cases in each group was 164 cases (two risk alleles), 330 cases (one risk allele), and 281 cases (zero risk allele). The mean age at examination for homozygous carriers of the LOC387715 risk allele was significantly lower (73.9 years) than the age for carriers of one (76.4 years) or no (77.1 years) risk allele (P = .0003). Of the 16 features analyzed, only AMD grade (P = .00002) was significantly associated with the LOC387715 variant. As the number of LOC387715 risk alleles increased, the proportion of grade 5 AMD cases increased in a dose-response fashion. CONCLUSIONS: The LOC387715 variant appears to be an independent risk factor for grade 5 (neovascular) AMD. This variant may also be associated with an earlier onset of AMD. Phenotypes that suggest a high-risk genotype may prove valuable for diagnostic, therapeutic, and research purposes.

Duke Scholars

Author Michael Arthur Hauser Medicine, Medical Genetics