title: Copy number variations in candidate genes in neovascular age-related macular degeneration.
abstract: OBJECTIVE
  The pathogenesis of age-related macular degeneration (AMD) is strongly influenced by genetic factors, and single nucleotide polymorphisms have been consistently linked to AMD. Copy number variation (CNV), or variation in the number of copies of a particular segment of DNA, may also contribute to AMD pathogenesis. This study evaluated CNVs in candidate genes that have been reported to be linked to AMD.
  
  
  METHODS
  Study participants were 131 patients with neovascular AMD and 103 elderly persons without AMD who were evaluated by retinal specialists at the National Eye Institute. DNA was collected from peripheral whole blood, and duplex RT-PCR based copy number (CN) assays were performed for the genes CCR3, CFH, CX3CR1, ERCC6, HTRA1, and VEGF. Quantitative CNs (CN = 0, 1, 2, or 3+) were determined.
  
  
  RESULTS
  Novel CNVs were discovered in CCR3, CX3CR1, and ERCC6. The unadjusted data suggested that CN = 3+ for CX3CR1 might be mildly protective against AMD, but this trend did not persist after adjustment for age. AMD patients appeared to have an elevated mean CFH CN relative to controls (2.13 [95% confidence interval (CI), 2.05-2.21] vs. 2.01 [95% CI, 1.92-2.09 copies]; P = 0.05). No significant associations between CNV and AMD were observed for the remaining genes.
  
  
  CONCLUSIONS
  The methods described are suitable for quantitative characterization of CNV in candidate genes. The authors identified CNVs in AMD-associated genes but did not find strong evidence for a link with neovascular AMD.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Liu
authors.forename: Elvira
authors.initials: E
authors.lastname: Agrón
authors.forename: Emily
authors.initials: E
authors.lastname: Chew
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyerle
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Tuo
mesh_terms: D000368:Aged; D000073883:CX3C Chemokine Receptor 1; D020256:Choroidal Neovascularization / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D000075223:Poly-ADP-Ribose Binding Proteins; D054397:Receptors, CCR3 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C515350:CCR3 protein, human; C493495:CFH protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D005136:Eye Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes