title: Involvement of genetic variants associated with primary open-angle glaucoma in pathogenic mechanisms and family history of glaucoma.
abstract: OBJECTIVE
  To investigate the associations between the non-intraocular pressure (IOP)-related genetic variants (genetic variants associated with vulnerability of the optic nerve independent of IOP) and primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG) and high-tension glaucoma (HTG), and between the non-IOP-related genetic variants and a family history of glaucoma.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Japanese patients with NTG (n = 213) and HTG (n = 212) and 191 control subjects were genotyped for 5 non-IOP-related genetic variants predisposing to POAG near the SRBD1, ELOVL5, CDKN2B/CDKN2B-AS1, SIX1/SIX6, and ATOH7 genes. The load of these genetic variants was compared between the control subjects and patients with NTG or HTG and between the POAG patients with and without a family history of glaucoma.
  
  
  RESULTS
  The total number of POAG risk alleles and the product of the odds ratios (POAG risk) of these genetic variants were significantly larger (P < .0025) in patients with both NTG and HTG than in the control subjects, and were significantly larger (P = .0042 and P = .023, respectively) in POAG patients with a family history of glaucoma than in those without. As the number of relatives with glaucoma increased, the total number of risk alleles and the product of the odds ratios increased (P = .012 and P = .047, respectively).
  
  
  CONCLUSIONS
  Non-IOP-related genetic variants contribute to the pathogenesis of HTG as well as NTG. A positive family history of glaucoma in cases of POAG is thought to reflect the influence of genetic variants predisposing to POAG.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. Electronic address: fmabuchi@yamanashi.ac.jp.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Mabuchi
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakurada
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashiwagi
authors.affiliation: Department of Health Sciences, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Zentaro
authors.initials: Z
authors.lastname: Yamagata
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Tsukahara
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D040741:Genetic Load; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics; D007564:Japan; D057066:Low Tension Glaucoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014065:Tonometry, Ocular