title: Associations of the C2-CFB-RDBP-SKIV2L locus with age-related macular degeneration and polypoidal choroidal vasculopathy.
abstract: OBJECTIVE
  To investigate the associations of the C2-CFB-RDBP-SKIV2L region with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).
  
  
  METHODS
  Cross-sectional, case-control association study.
  
  
  METHODS
  A Chinese case-control group of 200 neovascular AMD patients, 233 PCV patients, and 275 control subjects.
  
  
  METHODS
  An association analysis was performed of the C2-CFB-RDBP-SKIV2L locus with both neovascular AMD and PCV in a Chinese population using 19 haplotype-tagging single nucleotide polymorphisms (SNPs) and 6 previously reported SNPs across the C2-CFB-RDBP-SKIV2L region. All SNPs were genotyped using the TaqMan genotyping technology (TaqMan; Applied Biosystems [ABI], Foster City, CA).
  
  
  METHODS
  Allele and haplotype frequencies of the SNPs in the C2-CFB-RDBP-SKIV2L region.
  
  
  RESULTS
  The SKIV2L SNPs rs429608 and rs453821 were significantly associated with neovascular AMD (P = 7.39 × 10(-5); odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.50; and P = 0.001; OR, 0.38; 95% CI, 0.21-0.70, respectively), whereas borderline associations were detected for C2 rs547154 (P = 0.002) and RDBP rs760070 (P = 0.003). Conditional haplotype analysis revealed that SKIV2L rs429608 could account fully for the global haplotype association identified in this region. The association of SKIV2L rs429608 with neovascular AMD remained significant after adjusting for CFH rs800292 and HTRA1 rs11200638. No individual SNP or haplotype was associated significantly with PCV.
  
  
  CONCLUSIONS
  In this concurrent investigation of the associations of the entire C2-CFB-RDBP-SKIV2L region with neovascular AMD and PCV, the results suggested that SKIV2L is a likely causal gene for neovascular AMD, conferring a significant protective effect independent of CFH and HTRA1. These data do not support a significant role of this region in PCV, suggesting different molecular mechanisms between neovascular AMD and PCV.
authors.affiliation: Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.forename: Li Jia
authors.initials: LJ
authors.lastname: Chen
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Timothy Y Y
authors.initials: TY
authors.lastname: Lai
authors.forename: David T L
authors.initials: DT
authors.lastname: Liu
authors.forename: Sylvia W Y
authors.initials: SW
authors.lastname: Chiang
authors.forename: Mingming
authors.initials: M
authors.lastname: Yang
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002681:China / Q000453:epidemiology; D020256:Choroidal Neovascularization / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D004247:DNA; D004265:DNA Helicases; C114718:SKIV2L protein, human