title: Complement factor D in age-related macular degeneration.
abstract: OBJECTIVE
  To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females.
  
  
  CONCLUSIONS
  CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis.
authors: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom.
authors: Chloe M
authors: CM
authors: Stanton
authors: John R W
authors: JR
authors: Yates
authors: Anneke I
authors: AI
authors: den Hollander
authors: Johanna M
authors: JM
authors: Seddon
authors: Anand
authors: A
authors: Swaroop
authors: Dwight
authors: D
authors: Stambolian
authors: Sascha
authors: S
authors: Fauser
authors: Carel
authors: C
authors: Hoyng
authors: Yi
authors: Y
authors: Yu
authors: Kanda
authors: K
authors: Atsuhiro
authors: Kari
authors: K
authors: Branham
authors: Mohammad
authors: M
authors: Othman
authors: Wei
authors: W
authors: Chen
authors: Elod
authors: E
authors: Kortvely
authors: Kevin
authors: K
authors: Chalmers
authors: Caroline
authors: C
authors: Hayward
authors: Anthony T
authors: AT
authors: Moore
authors: Baljean
authors: B
authors: Dhillon
authors: Marius
authors: M
authors: Ueffing
authors: Alan F
authors: AF
authors: Wright
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D011416:Complement Factor D / Q000235:genetics / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000502:physiology*; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C493488:CFD protein, human; D011416:Complement Factor D