title: Progression of geographic atrophy and genotype in age-related macular degeneration.
abstract: OBJECTIVE
  We sought to determine whether genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD).
  
  
  METHODS
  Prospective analysis of participants in a randomized controlled clinical trial.
  
  
  METHODS
  We included 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS).
  
  
  METHODS
  Fundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed.
  
  
  METHODS
  Genotype frequencies and change in cumulative area of GA.
  
  
  RESULTS
  The mean growth rate of GA for the 114 eyes was 1.79 mm(2)/year (range, 0.17-4.76). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3 genes. For the single nucleotide polymorphism rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared with the homozygous nonrisk genotype (unadjusted P = 0.002; Bonferroni-corrected P = 0.014) and for allelic association (Bonferroni-corrected P value = 0.011). Analyses of other measures of GA progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype.
  
  
  CONCLUSIONS
  Growth rates of GA calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, or TLR3 genes. There was a nominally significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations is needed to establish the existence of an association.
authors.affiliation: Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, and Devers Eye Institute, Portland, Oregon 97239, USA. kleinm@ohsu.edu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Francis
authors.forename: Anne S
authors.initials: AS
authors.lastname: Lindblad
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.forename: Sara C
authors.initials: SC
authors.lastname: Hamon
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D003175:Complement C2 / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D057092:Geographic Atrophy / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics
chemical_list: C514392:ARMS2 protein, human; D001057:Apolipoproteins E; C493495:CFH protein, human; D003175:Complement C2; D003176:Complement C3; D011506:Proteins; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D017242:Complement Factor H
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