title: The ARMS2 A69S variant and bilateral advanced age-related macular degeneration.
abstract: OBJECTIVE
  To identify genetic associations between specific risk genes and bilateral advanced age-related macular degeneration (AMD) in a retrospective, observational case series of 1,003 patients: 173 patients with geographic atrophy in at least 1 eye and 830 patients with choroidal neovascularization in at least 1 eye.
  
  
  METHODS
  Patients underwent clinical examination and fundus photography. The images were subsequently graded using a modified grading system adapted from the Age-Related Eye Disease Study. Genetic analysis was performed to identify genotypes at 4 AMD-associated variants (ARMS2 A69S, CFH Y402H, C3 R102G, and CFB R32Q) in these patients.
  
  
  RESULTS
  There were no statistically significant relationships between clinical findings and genotypes at CFH, C3, and CFB. The genotype at ARMS2 correlated with bilateral advanced AMD using a variety of comparisons: unilateral geographic atrophy versus bilateral geographic atrophy (P = 0.08), unilateral choroidal neovascularization versus bilateral choroidal neovascularization (P = 9.0 × 10(-8)), and unilateral late AMD versus bilateral late AMD (P = 5.9 × 10(-8)).
  
  
  CONCLUSIONS
  In this series, in patients with geographic atrophy or choroidal neovascularization in at least 1 eye, the ARMS2 A69S substitution strongly associated with geographic atrophy or choroidal neovascularization in the fellow eye. The ARMS2 A69S substitution may serve as a marker for bilateral advanced AMD.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. sschwartz2@med.miami.edu
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Schwartz
authors.forename: Anita
authors.initials: A
authors.lastname: Agarwal
authors.forename: Jaclyn L
authors.initials: JL
authors.lastname: Kovach
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gallins
authors.forename: William
authors.initials: W
authors.lastname: Cade
authors.forename: Eric A
authors.initials: EA
authors.lastname: Postel
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Ayala-Haedo
authors.forename: Kylee M
authors.initials: KM
authors.lastname: Spencer
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D057092:Geographic Atrophy / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D003176:Complement C3; D011506:Proteins; D017242:Complement Factor H; D011415:Complement Factor B