Variants in optineurin gene and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma

Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4359-67. doi: 10.1167/iovs.03-1403.


Purpose: To investigate sequence variations in the optineurin (OPTN) gene and their association with TNF-alpha polymorphisms in Japanese patients with glaucoma.

Methods: The OPTN gene was analyzed in blood samples from 629 Japanese subjects. There were 194 patients with primary open-angle glaucoma (POAG), 217 with normal-tension glaucoma (NTG), and 218 with no eye disease (control subjects). The gene was screened for mutations by denaturing high-performance liquid chromatography. Genotyping of three polymorphisms of -308G-->A, -857C-->T, and -863C-->A in the TNF-alpha promoter region was performed. The associations between the genotypes and age, intraocular pressure (IOP), and visual field defects at the time of diagnosis were examined.

Results: A possible glaucoma-causing mutation, His26Asp, was identified in 1 of the 411 Japanese patients with glaucoma. A c.412G-->A (Thr34Thr) polymorphism in the OPTN gene was significantly associated with POAG (genotype frequency, P = 0.011; allele frequency, P = 0.003). The frequency of TNF-alpha/-857T and optineurin/412A carriers was significantly higher (P = 0.006) in patients with POAG than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-857T, the optineurin/412A carriers had significantly worse (P = 0.020) visual field scores than the non-optineurin/412A ones. The frequency of TNF-alpha/-863A and optineurin/603A (or Lys98) carriers was significantly higher in patients with POAG (P = 0.008) or NTG (P = 0.027) than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-863A, the ones with optineurin/603A (or Lys98) had significantly worse (P = 0.026) visual field scores than did those with non-optineurin/603A (or Lys98).

Conclusions: These findings demonstrated that the OPTN gene is associated with POAG rather than NTG in the Japanese. Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-alpha genes that would increase the risk for glaucoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging
  • Alleles
  • Asian People / genetics*
  • Aspartic Acid
  • Cell Cycle Proteins
  • Chromatography, High Pressure Liquid
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / physiopathology
  • Heterozygote
  • Histidine
  • Humans
  • Intraocular Pressure*
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Mutation
  • Polymorphism, Genetic*
  • Threonine
  • Transcription Factor TFIIIA / genetics*
  • Tumor Necrosis Factor-alpha / genetics*
  • Visual Fields


  • Cell Cycle Proteins
  • Membrane Transport Proteins
  • OPTN protein, human
  • Transcription Factor TFIIIA
  • Tumor Necrosis Factor-alpha
  • Threonine
  • Aspartic Acid
  • Histidine