Precursors of age-related macular degeneration: associations with vitamin A and interaction withCFHY402Hin the Inter99 Eye Study

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To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms incomplement factor H(CFHY402H)andARMS2/LOC387715.


Cross-sectional study of 848 subjects aged 30–60 years from the Inter99 Eye Study. Daily intake of vitamins and minerals was estimated from a 198-item food frequency questionnaire. Digital fundus photographs were recorded in red-free illumination and graded for macular drusen >63μm and numerous (>20) small hard macular drusen as a mean of both eyes.


Higher intake of vitamin A increased the risk of having macular drusen >63μm with odds ratio = 1.82 (CI95 1.02–3.24, p = 0.042) comparing participants in the highest quartile of vitamin A intake with participants in the lowest quartile, adjusted for recruitment group, age and sex. There was a significant interaction withCFHY402H(p = 0.038). Among 504 participants withCFHY402H, the relative risk of having macular drusen >63μm was increased in participants in the highest quartile of vitamin A intake (odds ratio = 2.58; CI95 1.16–5.73, p = 0.020) and in the second highest quartile (odds ratio = 3.27; CI95 1.50–7.13, p = 0.0029) compared with the lowest quartile. Further adjusting for total fat intake, energy intake, plasma cholesterol, body mass index (BMI), smoking, alcohol intake, education and physical activity strengthened the association.


In this cross-sectional study, a higher intake of vitamin A increased the risk of macular drusen >63μm in subjects withCFHY402H. The study supports that vitamin A may be a risk factor for early AMD.

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