title: Analysis of the Y402H variant of the complement factor H gene in age-related macular degeneration.
abstract: OBJECTIVE
  Recent studies in U.S. populations have indicated that the Y402H variant of the complement factor H (CFH) gene contains a major risk susceptibility allele for age-related macular degeneration (AMD). This study was conducted to ascertain whether this is also true in a non-U.S. population and also whether the at-risk allele is associated with the clinical phenotype of disease and the age at diagnosis.
  
  
  METHODS
  Two hundred thirty-six unrelated individuals with AMD and 144 unrelated but ethnically matched control subjects were recruited and examined. All subjects completed a standard questionnaire, were given a fundus examination, and provided a blood sample for DNA extraction. Alleles of Y402H in the CFH gene were determined by use of a MALDI-TOF-based approach followed by statistical analysis.
  
  
  RESULTS
  Individuals with AMD who had at least one copy of the C allele of Y402H had an increased risk of disease (odds ratio [OR] 2.98; 95% confidence interval [CI] 1.81-4.93) compared with cases with the T allele. On subgroup analysis, this risk was found to be most significant in individuals with neovascular disease (OR 4.34; 95% CI 1.94, 9.71). In addition, individuals with neovascular disease who were homozygous CC presented with a significant 7.0-year earlier age at diagnosis relative to those individuals who were homozygous TT. The population-attributable risk for the C allele ranged between 47% to 69%, depending on the AMD disease subtype.
  
  
  CONCLUSIONS
  The C allele of Y402H represents a significant risk factor in individuals with AMD, and this effect is most pronounced in individuals with neovascular disease.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria. pnb@unimelb.edu.au
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.forename: F M Amirul
authors.initials: FM
authors.lastname: Islam
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.forename: Melinda
authors.initials: M
authors.lastname: Cain
authors.forename: Nicola
authors.initials: N
authors.lastname: Hunt
authors.forename: Robyn
authors.initials: R
authors.lastname: Guymer
mesh_terms: D000368:Aged; D000483:Alleles; D017242:Complement Factor H / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D011795:Surveys and Questionnaires
chemical_list: D017242:Complement Factor H