title: Complement factor H polymorphism p.Tyr402His and cuticular Drusen.
abstract: OBJECTIVE
  To determine the histidine frequency in patients with the cuticular drusen phenotype of age-related macular degeneration (AMD).
  
  
  METHODS
  Fifty individuals were identified who met the criteria for the cuticular drusen phenotype using a standard threshold photograph. We genotyped DNA samples using a polymerase chain reaction-based restriction digest assay. Seven hundred individuals with typical AMD and 252 controls were also genotyped. Fisher exact test was used to analyze the significance of allele frequency differences.
  
  
  RESULTS
  The histidine variant was present in 70% (frequency +/- SE, 0.70 +/- 0.05) of the cuticular cohort, 55% (frequency +/- SE, 0.55 +/- 0.01) of the more typical AMD cases, and 34% (frequency +/- SE, 0.34 +/- 0.02) of controls. The association between the cuticular drusen phenotype and the histidine allele was highly significant (P = .003; odds ratio, 2.0; 95% confidence interval, 1.21-3.07; vs AMD cases P<.001; odds ratio 4.54; 95% confidence interval, 2.79-7.50; vs controls). Genotype distribution between the 3 groups was similarly significant (P<.001).
  
  
  CONCLUSIONS
  The cuticular drusen phenotype is highly associated with the Tyr402His variant of the complement factor H (CFH) gene. The significantly higher histidine allele frequency in this group compared with the typical AMD cohort suggests that the complement cascade may play a greater role in the pathogenesis of the cuticular drusen subtype than in AMD as a whole.
  
  
  CONCLUSIONS
  The c.1204T>C, p.Tyr402His allelic variant in the CFH gene is associated with a 3-fold increased risk for AMD. A high frequency of the histidine allele has also been noted in patients with membranoproliferative glomerulonephritis type II.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grassi
authors.forename: James C
authors.initials: JC
authors.lastname: Folk
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.forename: Christine M
authors.initials: CM
authors.lastname: Taylor
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015593:Retinal Drusen / Q000235:genetics*
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H