April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Genetic Data Suggest a Novel Association Between the Vitamin D Pathway and Neovascular Age-Related Macular Degeneration
Author Affiliations & Notes
  • A. C. Silveira
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • M. A. Morrison
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • J. W. Miller
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • I. K. Kim
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • D. A. Schaumberg
    Preventive Med 3rd F, Brigham & Womens Hosp/Harvard, Boston, Massachusetts
  • B. W. Hollis
    Pediatric Nutritional Sciences, Medical University of South Carolina, Charleston, South Carolina
  • R. Chen
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
  • G. S. Hageman
    Ophthalmology & Visual Sciences, University of Iowa Hospitals & Clinics, Coralville, Iowa
  • M. M. DeAngelis
    Dept of Ophthalmology, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  A.C. Silveira, None; M.A. Morrison, None; J.W. Miller, None; I.K. Kim, None; D.A. Schaumberg, None; B.W. Hollis, None; R. Chen, None; G.S. Hageman, None; M.M. DeAngelis, None.
  • Footnotes
    Support  The Lincy Foundation, the Knight AMD Fund, the Mass. Lions, Friends of the MEEI, Genetics of AMD Fund, Research to Prevent Blindness, NIH grants EY014458, EY14104, and EY017362.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2478. doi:https://doi.org/
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      A. C. Silveira, M. A. Morrison, J. W. Miller, I. K. Kim, D. A. Schaumberg, B. W. Hollis, R. Chen, G. S. Hageman, M. M. DeAngelis; Genetic Data Suggest a Novel Association Between the Vitamin D Pathway and Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2478. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Preliminary data from our laboratory suggest a protective role for lifetime UV exposure in susceptibility to age-related macular degeneration (AMD). Thus, we evaluated the genetic contribution of variation in vitamin D pathway genes and serum vitamin D levels to neovascular AMD.

Methods: : Fifty-nine tagging SNPs in the vitamin D metabolism pathway genes VDR, CYP27B1, CYP24A1, and CYP27A1 were genotyped in 135 extremely discordant sibling pairs (>50 years of age) where one sibling had neovascular disease and the other sibling was AMD-free. Single SNPs and haplotypes were tested for association using FBAT. Haplotypes were constructed in a backwards step-wise selection method with SNPs that were p<0.12. Significant variation was tested for interaction with CFH, ARMS2/HTRA1, and smoking. A subset of 50 pairs from this cohort were ascertained for vitamin D serum levels.

Results: : Sera analyses showed a slight trend of higher vitamin D levels in unaffected siblings. After controlling for age, sex, smoking, CFH, and ARMS2/HTRA1 only variation in CYP24A1 influenced AMD risk. After permutation testing, the most significantly associated haplotype increased risk for neovascular AMD (p = 2 x 10-5). No interaction was found between variation in CYP24A1 and CFH, ARMS2/HTRA1, and smoking.

Conclusions: : This is the first report that demonstrates a genetic association between the vitamin D pathway gene CYP24A1 and neovascular AMD. Based on the slight trend towards higher serum vitamin D levels in unaffected patients, vitamin D serum levels are being assayed in an expanded cohort. Studies utilizing next generation sequencing technology to pinpoint disease causality with subsequent validation in unrelated case-control and prospectively based nested case-control cohorts are ongoing.

Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: risk factor assessment • gene screening 

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