Abstract

DO.18.07

Is there a specific relationship between early AMD and polymorphisms in the CFH- and ARMS2-gene? – A genotype/phenotype-analysis

Martha Dietzel1, Astrid Farwick2, Britta E. Heimes1, Bodo Neuner2, Daniel Pauleikhoff1, Hans-Werner Hense2
1Augenabteilung am St. Franziskus-Hospital Münster; 2Institut für Epidemiologie und Sozialmedizin, Westfälische Wilhelms-Unversität Münster

Objective: Different studies have shown a highly significant association of specific polymorphisms in the CFH- and ARMS2-gene with appearance of AMD. Further, the clinical AREDS study demonstrated a significant increment of ten-year risk of developing late AMD with increasing severity of early AMD (AREDS scores 0-4). In order to analyse the relationship between different stages of early AMD, especially characteristics of drusen, and polymorphisms associated with elevated risk for AMD in the CFH- (SNP rs1061170) and ARMS2-gene (SNP rs10490924) a genotype-phenotype analysis was conducted in the Münster Aging and Retina Study (MARS).
Methods: In the MARS study characteristics of drusen in a central grid (diameter: 6000µm) were detected in 593 patients with AMD and 170 controls on the basis of fundus photographs with regard to size, number and confluence. The stages of AMD were defined corresponding to the classification of AREDS (scores 0-4). The collected features of drusen and stages of AMD were analysed with regard to relationships with polymorphisms in the CFH- and ARMS2-gene.
Results: A highly significant relationship between increasing levels of AMD and appearance of polymorphisms associated with elevated risk for AMD in the CFH- and ARMS2-gene could be shown (p<0.001 each). Thereby in probands with very early AMD (score "1") only the polymorphism in the CFH-gene occurred significantly more often than in controls. Analysing specific characteristics of early AMD a significant relationship was detected between size of drusen (controls vs. <63 µm vs. >175 µm) and polymorphism of risk in the CFH- and ARMS2-genes (p<0.01 each). Likewise a significant relation was found between number of drusen (controls vs. <20 vs. ≥20 Drusen) respectively confluence of drusen (controls vs. <10% vs. ≥50% confluence of drusen) and analysed polymorphisms (p<0.01 each).
Conclusions: The present study showed a clear and significant relationship between characteristics of early AMD and analysed polymorphisms associated with elevated risk for AMD in the CFH- and ARMS2-gene. These findings pronounce the impact of these polymorphisms especially in the occurrence of drusen within early AMD. Particularly large respectively confluent drusen seem to be genetically influenced. Pharmacologic intervention in the range of following products of these genes possibly might influence the risk of progression of AMD. Furthermore, characteristics of drusen could be consulted for efficacy of therapy.

Copyright: 2009 Porstmann Kongresse GmbH. All rights reserved. Impressum, Disclaimer.