title: Chronic central serous chorioretinopathy is associated with genetic variants implicated in age-related macular degeneration.
abstract: OBJECTIVE
  In this study, single nucleotide polymorphisms (SNPs) at 19 loci, previously associated with age-related macular degeneration (AMD), were systematically tested for association in patients with chronic central serous chorioretinopathy (cCSC). In addition, we evaluated the effect of detailed phenotyping on these genetic associations.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  We included 292 cCSC patients, 1147 AMD patients, and 1311 control individuals.
  
  
  METHODS
  We genotyped SNPs at 19 AMD-associated loci and 6 additional SNPs at the complement factor H (CFH) locus. Phenotyping of all patients was based on fundoscopy, spectral-domain optical coherence tomography, fluorescein angiography (FA), and indocyanine green angiography.
  
  
  METHODS
  We measured the allele frequencies of 25 AMD-associated SNPs and CFH haplotype frequencies in patients with cCSC and the effect of phenotypic subdivision of cCSC on genetic associations.
  
  
  RESULTS
  One SNP in ARMS2 (rs10490924) was significant after Bonferroni correction (Punadjusted=0.002; odds ratio [OR]=0.64). The SNPs at 3 other AMD loci (CFH, TNFRSF10A, ADAMTS9) showed a trend toward association with typical cCSC. Further analysis of the CFH locus identified 2 SNPs that significantly conferred increased risk for cCSC and 1 that was protective. The CFH-H3 haplotype was also found to be protective (P=0.01; OR=0.54). Using multimodal imaging, 197 patients were classified as having typical cCSC, 52 patients had unilateral abnormalities on FA that were otherwise typical of cCSC, and 43 patients had a clinical picture that could be compatible with cCSC, but with features that could also indicate other macular diseases. Significant differences of the minor allele frequencies of the tested SNPs were observed between these 3 phenotypic subgroups.
  
  
  CONCLUSIONS
  Chronic CSC is associated with genetic variants in ARMS2 and CFH, indicating a genetic and pathophysiologic overlap between cCSC and AMD. Intriguingly, alleles in ARMS2 and CFH that confer risk of AMD may be protective for cCSC, and alleles in CFH that are protective for AMD confer risk for cCSC. Significant differences in allele frequencies were found among the phenotypic subgroups for several SNPs, illustrating the importance of correct clinical classification.
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Eiko K
authors.initials: EK
authors.lastname: de Jong
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Myrte B
authors.initials: MB
authors.lastname: Breukink
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Rosa L
authors.initials: RL
authors.lastname: Schellevis
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Bakker
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Mohr
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Jan E E
authors.initials: JE
authors.lastname: Keunen
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.affiliation: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: C.J.F.Boon@lumc.nl.
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D056833:Central Serous Chorioretinopathy / Q000175:diagnosis / Q000235:genetics*; D002908:Chronic Disease; D004396:Coloring Agents; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005787:Gene Frequency; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D007208:Indocyanine Green; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009887:Ophthalmoscopy; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D004396:Coloring Agents; D011506:Proteins; D017242:Complement Factor H; D007208:Indocyanine Green