title: The involvement of complement factor B and complement component C2 in an Indian cohort with age-related macular degeneration.
abstract: OBJECTIVE
  Genes involved in the complement cascade such as complement factor B (CFB) and complement component C2 have been implicated in age-related macular degeneration (AMD) worldwide. In continuation of the analysis of CFH and LOC387715/HTRA1, this study was conducted to gain understanding of the role of CFB and C2 in an Indian AMD cohort.
  
  
  METHODS
  Single nucleotide polymorphisms in CFB and C2 were screened in a cohort of clinically well-characterized patients with AMD (n = 177) and unaffected normal control subjects (n = 175). Screening was accomplished by a combination of customized genotyping followed by validation through resequencing. In addition, genotyping of two CFB variants (rs12614 and rs641153) that were in close proximity had to be resolved by resequencing. Estimates of allele and genotype frequencies, odds ratios, Hardy-Weinberg equilibrium, linkage disequilibrium (LD), and haplotype frequencies were also performed.
  
  
  RESULTS
  Three SNPs in C2 (rs547154 [IVS10]; P = 5.4 x 10(-11)) and CFB (rs641153 [R32Q], P = 2.2 x 10(-7) and rs2072633 [IVS17]; P = 2.0 x 10(-4)) were strongly associated with reduced risk of AMD. The rs547154 and rs641153 were in strong LD (D' = 0.90, 95% CI = 0.81-0.96) and a protective haplotype T-A was observed (OR = 0.10, 95% CI = 0.05-0.20). LD was moderate (D' = 0.77, 95% CI = 0.67-0.85) between the rs547154 and the rs2072633 SNPs, and the haplotype T-T generated with these SNPs was relatively less protective (OR = 0.28, 95% CI = 0.18-0.44).
  
  
  CONCLUSIONS
  The results of the present study provide an independent validation of the association of rs547154 (C2) and rs641153 (CFB) SNPs with reduced risk of AMD in an Indian cohort.
authors.affiliation: Hyderabad Eye Research Foundation, Champalimaud Translational Centre, Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Hyderabad, India.
authors.forename: Inderjeet
authors.initials: I
authors.lastname: Kaur
authors.forename: Saritha
authors.initials: S
authors.lastname: Katta
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Reddy
authors.forename: Raja
authors.initials: R
authors.lastname: Narayanan
authors.forename: Annie
authors.initials: A
authors.lastname: Mathai
authors.forename: Ajit B
authors.initials: AB
authors.lastname: Majji
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D003175:Complement C2 / Q000235:genetics*; D011415:Complement Factor B / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: D003175:Complement C2; D011415:Complement Factor B