The OPA1 gene polymorphism is associated with normal tension and high tension glaucoma

Am J Ophthalmol. 2007 Jan;143(1):125-130. doi: 10.1016/j.ajo.2006.09.028. Epub 2006 Oct 23.


Purpose: To assess whether genetic polymorphisms of optic atrophy 1 (OPA1) are associated with primary open-angle glaucoma (POAG).

Design: Prospective case control association study.

Methods: Japanese patients with normal tension glaucoma (NTG, n = 194), and high tension glaucoma (HTG, n = 191), and 185 control subjects were analyzed for the OPA1 intervening sequence (IVS) 8+4 cystosine thymine (C/T) and IVS 8+32 thymine cystosine (T/C) polymorphisms using pyrosequencing technique.

Results: There was a significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the NTG patients and control subjects (P = .0074), and the frequency of the cystosine (C) allele was significantly higher in the NTG patients compared with the control subjects (19.3% vs 11.6%, P = .0036). Adjusted for age, gender, refractive error, and intraocular pressure, an almost two-fold increased risk of NTG (P = .004, odds ratio 2.27, 95% confidence interval 1.30 to 3.97) was found with the OPA1 IVS 8 +32 C allele. Although there was no significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the HTG patients and control subjects (P = .24), the age at the time of diagnosis (53 +/- 11.0 years, median value +/- median absolute deviation) in the HTG patients with the OPA1 IVS 8 +32 C allele was significantly younger than that (57 +/- 12.0 years) in the HTG patients without C allele (P = .048).

Conclusions: The OPA1 IVS 8 +32 T/C polymorphism is associated with NTG, and may be used as a marker for this disease association. This polymorphism also influences the phenotypic feature in patients with HTG and should be considered to be a genetic risk factor not only for NTG, but also for HTG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Female
  • GTP Phosphohydrolases / genetics*
  • Genetic Markers
  • Genotype
  • Glaucoma, Open-Angle / genetics*
  • Humans
  • Intraocular Pressure / genetics
  • Male
  • Middle Aged
  • Ocular Hypertension / genetics
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Prospective Studies
  • Risk Factors


  • Genetic Markers
  • GTP Phosphohydrolases
  • OPA1 protein, human