title: The contribution of genetic factors to phenotype and progression of drusen in early age-related macular degeneration.
abstract: OBJECTIVE
  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.
authors: Institute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1-D 3, 48129, Münster, Germany, martha.dietzel@uni-muenster.de.
authors: Martha
authors: M
authors: Dietzel
authors: Daniel
authors: D
authors: Pauleikhoff
authors: Astrid
authors: A
authors: Arning
authors: Britta
authors: B
authors: Heimes
authors: Albrecht
authors: A
authors: Lommatzsch
authors: Monika
authors: M
authors: Stoll
authors: Hans-Werner
authors: HW
authors: Hense
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D017242:Complement Factor H / Q000235:genetics; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D060005:Genotyping Techniques; D005858:Germany; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D015593:Retinal Drusen / Q000175:diagnosis / Q000235:genetics*; D044465:White People
chemical_list: C577836:ABCA1 protein, human; C514392:ARMS2 protein, human; D064286:ATP Binding Cassette Transporter 1; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H