title: Copy number variation of age-related macular degeneration relevant genes in the Korean population.
abstract: OBJECTIVE
  Studies that analyzed single nucleotide polymorphisms (SNP) in various genes have shown that genetic factors are strongly associated with age-related macular degeneration (AMD) susceptibility. Copy number variation (CNV) may be an additional type of genetic variation that contributes to AMD pathogenesis. This study investigated CNV in 4 AMD-relevant genes in Korean AMD patients and control subjects.
  
  
  METHODS
  Four CNV candidate regions located in AMD-relevant genes (VEGFA, ARMS2/HTRA1, CFH and VLDLR), were selected based on the outcomes of our previous study which elucidated common CNVs in the Asian populations. Real-time PCR based TaqMan Copy Number Assays were performed on CNV candidates in 273 AMD patients and 257 control subjects.
  
  
  RESULTS
  The predicted copy number (PCN, 0, 1, 2 or 3+) of each region was called using the CopyCaller program. All candidate genes except ARMS2/HTRA1 showed CNV in at least one individual, in which losses of VEGFA and VLDLR represent novel findings in the Asian population. When the frequencies of PCN were compared, only the gain in VLDLR showed significant differences between AMD patients and control subjects (p = 0.025). Comparisons of the raw copy values (RCV) revealed that 3 of 4 candidate genes showed significant differences (2.03 vs. 1.92 for VEGFA, p<0.01; 2.01 vs. 1.97 for CFH, p<0.01; 1.97 vs. 2.01, p<0.01 for ARMS2/HTRA1).
  
  
  CONCLUSIONS
  CNVs located in AMD-relevant genes may be associated with AMD susceptibility. Further investigations encompassing larger patient cohorts are needed to elucidate the role of CNV in AMD pathogenesis.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
authors.forename: Hyeong Gon
authors.initials: HG
authors.lastname: Yu
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics*; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; D015415:Biomarkers; D011506:Proteins; D011973:Receptors, LDL; C467484:VEGFA protein, human; C036053:VLDL receptor; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H; D004247:DNA