title: Complement factor H R1210C among Japanese patients with age-related macular degeneration.
abstract: OBJECTIVE
  To evaluate the genotype distribution of a rare age-related macular degeneration (AMD)-susceptibility variant, complement factor H (CFH) R1210C, among a large Japanese cohort with AMD.
  
  
  METHODS
  One thousand three hundred and sixty-four Japanese patients with neovascular AMD were evaluated. We screened for CFH R1210C (rs121913059) by genotyping with the Taqman method; the mutation was confirmed by Sanger sequencing. We also searched for this mutation in the human genome variant database, which contains the whole-exome sequencing data for 1208 Japanese individuals. The detailed characteristics of patients with this mutation were reviewed.
  
  
  RESULTS
  The mean age of the patients was 74.5 years (standard deviation 8.7); men accounted for 71.8 % of the patients. The CFH R1210C variant was found in only 1 of the 1364 AMD patients, and was heterozygous (minor allele frequency (MAF) = 0.037 %); it was not found in any of the 1208 individuals in the control group (MAF = 0 %). The patient with CFH R1210C was a 70-year-old woman whose main complaint was visual loss in the right eye. Dilated fundus examination, optical coherence tomography, and fluorescein and indocyanine angiography revealed polypoidal choroidal neovasculopathy (PCV), but no drusen in either eye. Despite treatment, her visual acuity had decreased to 1/50 by 6.8 years after her first visit.
  
  
  CONCLUSIONS
  The CFH R1210C variant was found to be rare among Japanese patients with AMD. The patient with the mutation did have the PCV subtype, but no drusen formation. Considering their ethnicity-specific nature, such rare variants should be studied by use of next-generation sequencing for each ethnicity.
authors.affiliation: Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Ophthalmology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan. yamashro@kuhp.kyoto-u.ac.jp.
authors.forename: Kenji
authors.identifier: http://orcid.org/0000-0001-9354-8558
authors.initials: K
authors.lastname: Yamashiro
authors.affiliation: Department of Ophthalmology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Tetsuju
authors.initials: T
authors.lastname: Sekiryu
authors.affiliation: Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000235:genetics*
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H
keywords: Age-related macular degeneration; Complement factor H; Genetics; R1210C; Rare variant