Abstract
Although various risk factors have been identified for the development of age-related macular degeneration (AMD), risk factors of early AMD have been relatively under studied. We aimed to investigate AMD risk factors by evaluating multiple factors in association with large drusen, an important component of AMD, simultaneously. In a community-based cross-sectional survey in Japan, 971 large drusen cases and 3,209 controls were compared for 65 variables, including systemic, environmental, and genetic factors. The association and the effect size of each factor were evaluated with logistic regression analysis using a backward-elimination approach. Multivariate analyses identified a significant association in serum calcium level (odds ratio [OR] = 0.932, P = 1.05 × 10−3), ARMS2 A69S (rs10490924) genotype (OR = 1.046, P < 0.001), Chlamydia pneumoniae IgG (OR = 1.020, P = 0.0440), and age (OR = 1.013, P < 0.001) for large drusen. Hypocalcemia was observed in 7.2% of large drusen cases and in 5.5% of controls (P = 0.0490). C. pneumoniae infections was more frequent in large drusen cases (56.4%) than in conrols (51.7%, P = 0.00956). These results suggest that calcium, ARMS2 genotype, C. pneumonia infection, and age are significant factors in the development of the early stages of AMD.
Highlights
Various risk factors have been identified for the development of age-related macular degeneration (AMD), risk factors of early AMD have been relatively under studied
A significant association was found between ARMS2 A69S and drusen; the frequency of the minor allele T, which is known as a risk allele for developing advanced AMD, was significantly higher in cases than in controls (P, 0.001)
We found that four of seven factors have a strong effect on the development of drusen: serum calcium level, ARMS2 A69S genotype, C. pneumoniae immunoglobulin G (IgG), and age
Summary
Various risk factors have been identified for the development of age-related macular degeneration (AMD), risk factors of early AMD have been relatively under studied. C. pneumoniae infections was more frequent in large drusen cases (56.4%) than in conrols (51.7%, P 5 0.00956) These results suggest that calcium, ARMS2 genotype, C. pneumonia infection, and age are significant factors in the development of the early stages of AMD. Age, smoking, and mutations in several genes are the most consistently identified risk factors for AMD1 These associations have been confirmed in populations across the globe, including Western and Asian countries[5,6,7,8,9]. We sought to simultaneously investigate multiple risk factors for large www.nature.com/scientificreports drusen, an important early sign of AMD that has been shown in many longitudinal studies to be predictive of incident AMD advanced[3,18], using a relatively large number of Japanese adults
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