title: Genotypic influences on severity of exudative age-related macular degeneration.
abstract: OBJECTIVE
  Major genetic risk factors have recently been identified for age-related macular degeneration (AMD), including the ARMS2/LOC387715 and CFH at-risk polymorphisms. The study was conducted to establish correlations between the AMD genotype and both the phenotype and severity of AMD.
  
  
  METHODS
  In a prospective cohort of 1216 AMD patients, four genotypic homozygous groups were identified (n = 264): double homozygous for wild-type alleles (group 1, n = 49), homozygous for the at-risk allele of ARMS2/LOC387715 only (group 2, n = 57), homozygous for the at-risk allele of CFH only (group 3, n = 106), and double homozygous for both at-risk alleles (group 4, n = 52). The phenotypic classification of exudative AMD was based on fluorescein angiography.
  
  
  RESULTS
  Mean age at presentation was significantly lower in group 4 than in group 1 (P < 0.014). Patients in group 4 presented more often with bilateral CNV and fibrovascular scars than did patients in group 1 (P < 0.001 and < 0.0031 respectively) and with significantly lower visual acuity (VA) in the first affected eye than did patients in group 1 (P < 0.02). Patients in group 2 presented with worse VA than did patients in group 3 (P < 0.003). Classic CNV was more commonly associated with the at-risk allele of the ARMS2/LOC387715 locus than with the at-risk allele of the CFH gene (P < 0.026).
  
  
  CONCLUSIONS
  This study demonstrates an association between the at-risk allele of the ARMS2/LOC387715 locus and classic CNV, fibrovascular lesions, and poor VA. Individuals double homozygous for both at-risk alleles had a higher risk of being affected with a severe form of AMD at an earlier age.
authors.affiliation: Faculté de Médecine Henri Mondor, Department of Ophthalmology, APHP (Assistance Publique Hôpitaux Paris), Groupe Hospitalier Albert Chenevier-Henri Mondor, University Paris 12, Créteil, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leveziel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Puche
authors.forename: Florence
authors.initials: F
authors.lastname: Richard
authors.forename: John E A
authors.initials: JE
authors.lastname: Somner
authors.forename: Jennyfer
authors.initials: J
authors.lastname: Zerbib
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bastuji-Garin
authors.forename: Salomon Y
authors.initials: SY
authors.lastname: Cohen
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Korobelnik
authors.forename: José
authors.initials: J
authors.lastname: Sahel
authors.forename: Gisèle
authors.initials: G
authors.lastname: Soubrane
authors.forename: Pascale
authors.initials: P
authors.lastname: Benlian
authors.forename: Eric H
authors.initials: EH
authors.lastname: Souied
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017242:Complement Factor H / Q000235:genetics; D005122:Exudates and Transudates; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D014792:Visual Acuity
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H