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Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration

Nature Genetics volume 20, pages 328–329 (1998)Cite this article

Age-related macular degeneration (AMD) is a potentially blinding disease that has been estimated to affect as many as 30% of people over age 65 (Refs 1,2). Clinical manifestations of AMD include deposition of debris within and beneath the retinal pigment epithelium (RPE), atrophy of the RPE and haemorrhage and exudation beneath the retina from aberrant choroidal blood vessels. The latter complication (sometimes referred to as 'wet' AMD) occurs in approximately 10% of eyes with AMD overall, but is present in approximately 90% of eyes that have become legally blind from this condition3. There is no evidence at this time that patients with this complication have a pathophysiologically distinct form of macular degeneration.

Recently, mutations in a gene (ABCR) encoding an ATP-binding transmembrane transporter protein have been associated with Stargardt disease4,5,6, an autosomal recessive retinal disease that, similar to AMD, affects the central retina (macula). Mutations in ABCR were later reported to be associated with up to 16% of AMD (ref. 7), although the methodology used in this study was controversial (http://www.sciencemag.org/cgi/content/full/279/5354/1107a). To further investigate the role of ABCR in Stargardt disease and AMD, we studied three populations: (i) 215 individuals with a clinical diagnosis of Stargardt disease; (ii) 182 patients with AMD diagnosed at the University of Iowa; and (iii) 96 unrelated subjects also from Iowa. The latter group was chosen to represent an ethnically matched sample of the population which would be expected to develop the population rate of AMD. Despite the loss of power, we decided not to choose an elderly, 'AMD free' control group, as this would require the subjective differentiation between the retinal changes involved in normal ageing and early AMD, a distinction which remains poorly understood. Sixty percent of the AMD group had, by the time of the study, developed a choroidal neovascular membrane in at least one eye. This rate of choroidal neovascularization is typical for a retina specialty clinic of a tertiary care hospital, and reflects the fact that the more severely affected AMD patients in a population are more likely to be cared for in such a venue than their less affected family members. Our study was designed to compare the three groups with respect to the proportion of non-conservative nucleotide changes present in each group. These were the same criteria we used in a similar study of MYOC in glaucoma8.

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Acknowledgements

We thank S. Jacobson, G. Fishman, R. Weleber and E. Héon for providing DNA samples from their Stargardt patients as well as for helpful discussions during the study. This work was supported in part by NIH grant EY10539, the Foundation Fighting Blindness, Research to Prevent Blindness, the Carver Charitable Trust, the Grousbeck Family Foundation, the Ruth and Milton Steinbach Foundation and the TFC Frost Trust (A.R.W.).

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Authors and Affiliations

  1. Department of Ophthalmology, The University of Iowa College of Medicine, Iowa City, Iowa, USA

    Edwin M. Stone., Andrew R. Webster, Kimberlie Vandenburgh, Luan M. Streb & Andrew J. Lotery

  2. Department of Pediatrics, The University of Iowa College of Medicine, Iowa City, Iowa, USA

    Robin R. Hockey & Val C. Sheffield

  3. The Howard Hughes Medical Institute, Iowa City, Iowa, USA

    Val C. Sheffield

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  1. Edwin M. Stone.
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  2. Andrew R. Webster
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  3. Kimberlie Vandenburgh
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Correspondence to Edwin M. Stone..

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Stone., E., Webster, A., Vandenburgh, K. et al. Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration. Nat Genet 20, 328–329 (1998). https://doi.org/10.1038/3798

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