Association of complement factor H tyrosine 402 histidine genotype with posterior involvement in sarcoid-related uveitis

Am J Ophthalmol. 2013 Jun;155(6):1068-1074.e1. doi: 10.1016/j.ajo.2013.01.019. Epub 2013 Mar 14.


Purpose: To determine whether the complement factor H (CFH) tyrosine 402 histidine (Y402H) variant, recently shown to be associated with age-related macular degeneration (AMD) and multifocal choroiditis, is associated with specific ocular sarcoidosis clinical phenotypes in black and white persons.

Design: Case-control study.

Methods: The CFH Y402H polymorphism (rs1061170) was genotyped in 41 subjects with ocular sarcoidosis and 393 control subjects. Allele frequencies in the ocular sarcoidosis cases were compared with controls using chi-square score tests. Genotypic model-based (dominant, recessive, and additive) associations of the rs1061170 allele were tested using multivariate logistic regression. Bayesian information criteria were used to formalize model selection. Genotypes were correlated with disease characteristics and severity of ocular inflammation.

Results: The C allele (rs1061170) was found in 35% of controls, but occurred with a significantly higher frequency (48.7%) in ocular sarcoidosis cases (odds ratio, 1.72; 95% confidence interval, 1.09 to 2.78; P = .018). Logistic regression demonstrated an association between rs1061170 and ocular sarcoidosis in 2 of 3 genetic models (additive, P = .0078; recessive, P = .0018). Posterior uveitis and panuveitis were overrepresented significantly in cases with the homozygous variant genotype (CC, 91%; P = .047). The population-attributable risk related to this CFH risk variant was 20%.

Conclusions: The Y402H polymorphism of CFH seems to be associated with ocular sarcoidosis in black and white persons. Carriage of the CFH Y402H polymorphism in both alleles is associated with an increased risk for posterior uveitis and panuveitis presentation. The prognostic importance of this genotype will require prolonged follow-up studies.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Black People / genetics
  • Case-Control Studies
  • Complement Factor H / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Genotyping Techniques
  • Histidine
  • Humans
  • Male
  • Middle Aged
  • Panuveitis / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Sarcoidosis / genetics*
  • Tyrosine
  • Uveitis, Posterior / genetics*
  • White People / genetics


  • CFH protein, human
  • Tyrosine
  • Histidine
  • Complement Factor H