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The contribution of genetic factors to phenotype and progression of drusen in early age-related macular degeneration

  • Genetics
  • Published:
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Abstract

Purpose

Genetic factors contribute to the development and progression of age-related macular degeneration (AMD). We aimed to assess the association of drusen as phenotypic characteristics of early AMD and their progression with polymorphisms in the CFH, ABCA1, and ARMS2 genes.

Methods

In the Münster Aging and Retina Study (MARS), drusen were detected in 406 patients with early AMD and 170 healthy controls according to the International Classification using fundus photographs, with a follow-up examination after 2.6 years (median). Six drusen features were assessed: drusen number (</≥20); confluence of drusen (</≥50 %), largest drusen size (</≥175 μm); area occupied by drusen (</≥10 %); most frequent drusen size (</≥175 μm), and presence of soft, indistinct drusen (no/yes). Based on these features, an unweighted summary drusen severity score (DSS; categorized in “low”, “intermediate” and “high”) was calculated. The relationship of each drusen feature and the DSS with CFH rs1061170, ABCA1 rs1883025, and ARMS2 rs10490924 at baseline and after 2.6 years was analyzed using multivariate logistic regression models.

Results

Cross-sectionally, each drusen feature was associated with a higher frequency of the CFH and ARMS2 risk variants. Compared to healthy eyes, the CFH risk variant was more common in eyes with early as well as advanced drusen features, while the ARMS2 variant was only associated with advanced drusen. After 2.6 years, 43 % of the eyes showed a progression of at least 1 unit in the DSS. The progression from low to higher DSS was inversely associated with ABCA1 (OR = 0.54), and the progression from intermediate to high DSS was positively related to CFH rs1061170 (OR = 2.3; p < 0.05 for each).

Conclusions

Variants in CFH, ABCA1, and ARMS2 genes are related to the presence and progression of drusen in early AMD. CFH and, inversely, ABCA1 seem to be involved in early drusen development, while the role of ARMS2 is more pronounced in advanced stages of early AMD.

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Disclosure

The authors declare that they have no conflict of interest.

Grant information

The study was supported by grants from Deutsche Forschungsgemeinschaft HE 2293/5-1, 5-2, 5-3 and PA 357/7-1; the Intramural Fund (IMF) of the Medical Faculty of the University of Münster; the Pro Retina Foundation; and the Jackstaedt Foundation.

A financial relationship with the organisations that sponsored the research does not exist. The authors have full control of all primary data and agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.

Author information

Authors and Affiliations

  1. Institute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1–D 3, 48129, Münster, Germany

    Martha Dietzel & Hans-Werner Hense

  2. Ophthalmology Department, St. Franziskus Hospital Münster, Hohenzollernring 74, 48145, Münster, Germany

    Martha Dietzel, Daniel Pauleikhoff, Britta Heimes & Albrecht Lommatzsch

  3. Genetic Epidemiology of vascular disorders, University of Münster, Domagkstr. 3, 48149, Münster, Germany

    Astrid Arning & Monika Stoll

Authors
  1. Martha Dietzel
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  2. Daniel Pauleikhoff
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  3. Astrid Arning
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  4. Britta Heimes
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  5. Albrecht Lommatzsch
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  6. Monika Stoll
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  7. Hans-Werner Hense
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Correspondence to Martha Dietzel.

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Dietzel, M., Pauleikhoff, D., Arning, A. et al. The contribution of genetic factors to phenotype and progression of drusen in early age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 252, 1273–1281 (2014). https://doi.org/10.1007/s00417-014-2690-7

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  • DOI: https://doi.org/10.1007/s00417-014-2690-7

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