title: Complement C3 variant and the risk of age-related macular degeneration.
abstract: BACKGROUND
  Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.
  
  
  METHODS
  We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.
  
  
  RESULTS
  The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9x10(-5)) and the Scottish group (244 cases and 351 controls, P=5.0x10(-5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.
  
  
  CONCLUSIONS
  Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom. jrwy1@cam.ac.uk
authors.forename: John R W
authors.initials: JR
authors.lastname: Yates
authors.forename: Tiina
authors.initials: T
authors.lastname: Sepp
authors.forename: Baljinder K
authors.initials: BK
authors.lastname: Matharu
authors.forename: Jane C
authors.initials: JC
authors.lastname: Khan
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thurlby
authors.forename: Humma
authors.initials: H
authors.lastname: Shahid
authors.forename: David G
authors.initials: DG
authors.lastname: Clayton
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Joanne
authors.initials: J
authors.lastname: Morgan
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Armbrecht
authors.forename: Baljean
authors.initials: B
authors.lastname: Dhillon
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Redmond
authors.forename: Alan C
authors.initials: AC
authors.lastname: Bird
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003176:Complement C3 / Q000737:chemistry / Q000235:genetics*; D003182:Complement C5 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D020836:Protein Structure, Quaternary
chemical_list: D003176:Complement C3; D003182:Complement C5