Association of Age-related Macular Degeneration (AMD) Susceptible Genes with Second Eye Involvement of AMD

Abstract

Purpose: In 2013, the largest genome-wide association study on age-related macular degeneration (AMD) identified 19 AMD susceptible loci, including 7 novel loci (The AMD Gene Consortium, Nature Genetics). Of these, ARMS2 was reported to be associated with the second eye involvement of AMD, while others have not been evaluated. In this study, we investigated whether these loci also associated with second eye involvement using relatively large Japanese cohort.

Methods: We retrospectively reviewed medical records of 513 patients who visited Macular Service at Department of Ophthalmology, Kyoto University Hospital for their unilateral AMD, and could be followed for at least 12 months. Written informed consent for genetic research had been obtained from all patients. All samples were genome-scanned using illumina OmniExpress or HumanOmni 2.5M. Survival analysis, log-rank test, and Cox proportional hazard regression analysis were used to examine the association between the genotypes of AMD susceptible single nucleotide polymorphisms (SNPs) and the duration until the development of AMD in the second eye.

Results: Mean follow-up period was 59.2±33.2 months. ARMS2 rs10490924 was significantly associated with fellow-eye involvement (P=0.0097; 10-year fellow-eye involvement rate GG:GT:TT = 12.0%:14.8%:42.1%). With regard to CFH rs800292, although patients with GG genotype (risk-homo) showed higher rate of second eye involvement, the association was not statistically significant (P=0.16; 10-year fellow-eye involvement rate AA:AG:GG = 11.5%:16.1%:27.9%). The 10-year fellow-eye involvement rate of the patients who had risk-homo genotype in both rs10490924 and rs800292 reached 57%, which was significantly (P=0.0015) higher than that of patients who had risk-homo genotype in either of the SNPs (19.9%) or that of patients who did not have risk-homo genotype in both SNPs (8.7%). The patients with 2 risk-homos showed 4.27 times as high risk of second-eye involvement as the patients with no risk-homo.

Conclusions: CFH rs800292 showed lower association with second-eye involvement than ARMS2 rs10490924. When patients had risk-homo genotype in both SNPs, 57% of them will develop AMD in fellow eye in 10 years.

Keywords: 412 age-related macular degeneration • 539 genetics