title: Haplotype analysis of the ARMS2/HTRA1 region in Japanese patients with typical neovascular age-related macular degeneration or polypoidal choroidal vasculopathy.
abstract: OBJECTIVE
  To compare the genomic contribution of the ARMS2/HTRA1 region of chromosome 10q26 to typical neovascular age-related macular degeneration (nAMD) (also known as typical exudative AMD) and to polypoidal choroidal vasculopathy (PCV) METHODS: DNA samples were prepared from 84 patients with typical nAMD, 181 patients with PCV, and 276 control participants. All of the 18 haplotype-tagging single-nucleotide polymorphisms (SNPs) derived from the HapMap data and the potential functional variant, rs11200638, which extended the ARMS2/HTRA1 region by 85.2 kb, were genotyped. Associations were tested using single-SNP and haplotype analyses.
  
  
  RESULTS
  Statistically significant associations were found for six of the 19 SNPs with both typical nAMD and PCV (P < 1 × 10(-3)), peaking at a segment containing three of the SNPs: rs3793917, rs10490924, and rs11200638 (P < 10(-7)). Six common haplotypes were inferred from the nine SNPs spanning 33 kb, which included the six SNPs associated with both phenotypes. Among the six common haplotypes, one showed a positive association with typical nAMD, and two, including the one mentioned above, were associated with PCV. In addition, they corresponded to the risk alleles rs10490924 and rs11200638.
  
  
  CONCLUSIONS
  The association pattern and haplotype estimation in the ARMS2/HTRA1 region of Japanese patients with PCV were very similar to those of Japanese patients with typical nAMD. The polymorphisms responsible for nAMD and PCV may be located in this region or in the strong linkage disequilibrium of rs10490924 and rs11200638.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
authors.forename: Norimoto
authors.initials: N
authors.lastname: Gotoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamashiro
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Saito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Iida
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D002829:Choroid / Q000098:blood supply; D015862:Choroid Diseases / Q000175:diagnosis / Q000235:genetics*; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006239:Haplotypes; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007564:Japan; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases