title: Genomic Copy Number Variations of the Complement Component C4B Gene Are Associated With Chronic Central Serous Chorioretinopathy.
abstract: OBJECTIVE
  Chronic central serous chorioretinopathy (cCSC) has recently been associated to variants in the complement factor H gene. To further investigate the role of the complement system in cCSC, the genomic copy number variations in the complement component 4 gene (C4) were studied.
  
  
  METHODS
  C4A and C4B copy numbers were analyzed in 197 cCSC patients and 303 healthy controls by using a Taqman copy number determination assay. Copy numbers of C4A, C4B, and the total C4 load were compared between cases and controls, by using a Fisher exact test. For this analysis Bonferroni correction was performed for three tests, and P values < 0.017 were considered to be significant. A logistic regression model was constructed to calculate the odds ratios (ORs) of each of the C4B copy numbers, using two copies as a reference. For this model P values < 0.05 were considered to be significant.
  
  
  RESULTS
  C4B genomic copy numbers differed significantly between cCSC patients and healthy controls (P = 0.0018). Absence of C4B significantly conferred risk of cCSC (P = 0.039, OR = 2.61 [95% confidence interval (CI) = 1.05-6.52]), whereas three copies of C4B significantly decreased the risk of cCSC (P = 0.014, OR = 0.45 [95% CI = 0.23-0.85]). The C4A genomic copy numbers and total C4 load did not significantly differ between cases and controls.
  
  
  CONCLUSIONS
  This study showed that copy numbers of C4B are significantly associated with cCSC. Carrying no copies of C4B significantly increases the risk of cCSC, whereas carrying three C4B copies is protective. These findings reinforce the hypothesis of a possible involvement of the complement system in the pathogenesis of cCSC.
authors: Department of Ophthalmology Radboud University Medical Center, Nijmegen, the Netherlands.
authors: Myrte B
authors: MB
authors: Breukink
authors: Department of Ophthalmology Radboud University Medical Center, Nijmegen, the Netherlands.
authors: Rosa L
authors: RL
authors: Schellevis
authors: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
authors: Camiel J F
authors: CJ
authors: Boon
authors: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors: Sascha
authors: S
authors: Fauser
authors: Department of Ophthalmology Radboud University Medical Center, Nijmegen, the Netherlands.
authors: Carel B
authors: CB
authors: Hoyng
authors: Department of Ophthalmology Radboud University Medical Center, Nijmegen, the Netherlands 4Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: Anneke I
authors: AI
authors: den Hollander
authors: Department of Ophthalmology Radboud University Medical Center, Nijmegen, the Netherlands.
authors: Eiko K
authors: EK
authors: de Jong
mesh_terms: D000328:Adult; D056833:Central Serous Chorioretinopathy / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002908:Chronic Disease; D015935:Complement C4b / Q000235:genetics* / Q000378:metabolism; D056915:DNA Copy Number Variations; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D041623:Tomography, Optical Coherence
chemical_list: D015935:Complement C4b