Calcium, ARMS2 genotype, and Chlamydia pneumoniae infection in early age-related macular degeneration: a multivariate analysis from the Nagahama study

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 controls (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.

Figure 1. The relative strength of the significant factors for large drusen that showed a significant association in the final multivariate analysis.

Serum calcium level had the strongest effect on the development of large drusen; the other factors were ARMS2 A69S (rs10490924) genotype, Chlamydia pneumoniae IgG, and age. High-density lipoprotein (HDL) cholesterol, α1-antitrypsin, and high-sensitivity C-reactive protein (hs-CRP) had limited effect on disease development with odds ratio between 1.000 and 1.001. A diamond represents the point estimate of odds ratio for each factor with a horizontal line of the 95% confidence interval (CI).