Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers

Invest Ophthalmol Vis Sci. 2006 Feb;47(2):536-40. doi: 10.1167/iovs.05-1143.


Purpose: The complement factor H (CFH) gene polymorphism Y402H (1277T-->C) has been associated with susceptibility to age-related macular degeneration (AMD). The purpose of this study was to confirm this association in a U.K. population, to determine whether the association holds for both geographic atrophy (GA) and choroidal neovascularization (CNV), and to investigate interactions with smoking.

Methods: A case-control study was undertaken in 443 cases of AMD, with 262 spouses as control subjects. All subjects completed a health and lifestyle questionnaire, had an ophthalmic assessment with fundus photography, and were genotyped.

Results: The frequencies of the C allele and CC genotype were significantly higher in cases than in controls. In comparison to the TT genotype, the odds ratios for AMD associated with the CT and CC genotypes were 3.1 (CI 2.0-4.6) and 6.3 (CI 3.8-10.4), respectively. The results were similar in subgroup analyses confined to cases with GA or CNV. The findings were also similar for subgroup analyses restricted to subjects who had never smoked, moderate smokers, or heavier smokers (>20 pack years of smoking). Heavier smokers with the CC genotype may be particularly at risk. The frequency of the CC genotype did not differ significantly between cases with and without a family history of AMD. There was no evidence that genotype had any influence on age at onset of disease.

Conclusions: The CFH Y402H variant is strongly associated with both GA and CNV in the U.K. population. This association is similar in smokers and nonsmokers. Heavier smokers with the CC genotype may be at particular risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Atrophy
  • Case-Control Studies
  • Choroidal Neovascularization / genetics*
  • Complement Factor H / genetics
  • Female
  • Gene Frequency
  • Genetic Variation
  • Genotype
  • Humans
  • Macular Degeneration / genetics*
  • Male
  • Photoreceptor Cells, Vertebrate / pathology*
  • Pigment Epithelium of Eye / pathology*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Smoking / genetics*


  • CFH protein, human
  • Complement Factor H