title: Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations.
abstract: We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).
  
  
  
  A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed.
  
  
  
  In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction.
  
  
  
  This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Marten E
authors.initials: ME
authors.lastname: Brelen
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Tsujikawa
authors.affiliation: Shantou University/The Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, China.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Wai Kit
authors.initials: WK
authors.lastname: Chu
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Timothy Y Y
authors.initials: TY
authors.lastname: Lai
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Danny S C
authors.initials: DS
authors.lastname: Ng
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sayanagi
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Chicako
authors.initials: C
authors.lastname: Hara
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hashida
authors.affiliation: Prince of Wales Hospital Eye Centre, Hong Kong, China.
authors.forename: Vesta C K
authors.initials: VC
authors.lastname: Chan
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China 4Prince of Wales Hospital Eye Centre, Hong Kong, China.
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Young
authors.affiliation: Shantou University/The Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China 3Shantou University/The Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, China.
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China 3Shantou University/The Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, China 4Prince of Wales Hospital Eye Centre, Hong Kong, China.
authors.forename: Li Jia
authors.initials: LJ
authors.lastname: Chen
mesh_terms: D000368:Aged; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism; D002829:Choroid / Q000098:blood supply / Q000473:pathology; D020256:Choroidal Neovascularization / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012160:Retina / Q000473:pathology; D057135:Wet Macular Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D017242:Complement Factor H; D004247:DNA