title: Complement factor B polymorphism 32W protects against age-related macular degeneration.
abstract: OBJECTIVE
  The 32Q (rs641153; A) and 32W (rs12614; T) variants of complement factor B (CFB) cause less efficient complement activation in vitro than the common 32R variant. This is thought to be the reason that the 32Q variant is associated with decreased risk of age-related macular degeneration (AMD). We investigated whether the 32W variant was also associated with decreased risk of AMD.
  
  
  METHODS
  We genotyped 367 cases with neovascular AMD and 251 disease-free controls. Association with the disease phenotype was assessed by logistic regression for polymorphisms of CFB alone and in combination with smoking status and genetic risk markers of complement factor H (CFH) and HtrA serine peptidase 1 (HTRA1). We performed meta-analysis of all previously published reports of 32W allele frequency in AMD cases and controls.
  
  
  RESULTS
  The CFB variant 32W was associated with protection against neovascular AMD, compared to the common 32R variant (odds ratio 0.64, p<0.05, in logistic regression with CFB variants; odds ratio 0.53, p<0.05, in logistic regression with CFB variants, CFH haplotypes, HTRA1 rs10490924 genotype, and smoking status). Meta-analysis (n=1,795) including this study and two others of neovascular AMD showed a combined odds ratio of 0.75 (p<0.05) for 32W, compared to 32R. Meta-analysis (n=2,600) of all reported studies of all types of AMD showed a combined odds ratio of 0.79 (p<0.01).
  
  
  CONCLUSIONS
  Our study shows that the 32W variant of CFB is associated with protection against AMD, in keeping with evidence of its functional effect on the complement system. The protective effect is less strong than that associated with 32Q.
authors.affiliation: Centre for Public Health, Queen's University Belfast, UK. a.hughes@qub.ac.uk
authors.forename: Anne E
authors.initials: AE
authors.lastname: Hughes
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Mullan
authors.forename: Declan T
authors.initials: DT
authors.lastname: Bradley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003167:Complement Activation; D011415:Complement Factor B / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism
chemical_list: D005973:Glutamine; D017242:Complement Factor H; D014364:Tryptophan; D001120:Arginine; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D011415:Complement Factor B