Analysis of the Y402H variant of the complement factor H gene in age-related macular degeneration

Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4194-8. doi: 10.1167/iovs.05-1285.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Complement Factor H / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Surveys and Questionnaires


  • Complement Factor H