Molecular genetic analysis of optineurin gene for primary open-angle and normal tension glaucoma in the Japanese population

J Glaucoma. 2004 Aug;13(4):299-303. doi: 10.1097/00061198-200408000-00007.


Purpose: To determine whether mutations in the optineurin (OPTN) gene are associated with the incidence of primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese.

Methods: Eighty-nine unrelated Japanese patients with POAG and 65 unrelated patients with NTG were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and thirteen exons of the OPTN gene were amplified by polymerase chain reaction (PCR) and directly sequenced.

Results: Sequence alterations in exons 4 (His26Asp), 5 (Met98Lys), and 16 (Arg545Gln) were found. The His26Asp and Arg545Gln mutations were not detected in 100 ethnically matched controls. The frequency of the missense Met98Lys variant was higher in the POAG and NTG groups than in the control group (16.9% versus 5%, 15.4% versus 5%; P = 0.009 and P = 0.029, and odds ratio 3.85 and 3.45, respectively, for the dominant effect of the OPTN A allele). Polymorphisms in exons 4 and 12, and in introns 6 and 7 were also detected.

Conclusions: The association of the allelic variation (Met98Lys) in the OPTN gene and the prevalence of POAG and NTG in unrelated Japanese patients suggest that they are involved in the pathogenesis of POAG and NTG.

MeSH terms

  • Aged
  • Alleles
  • Cell Cycle Proteins
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Glaucoma, Open-Angle / genetics*
  • Humans
  • Japan
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Molecular Biology
  • Mutation, Missense*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Transcription Factor TFIIIA / genetics*


  • Cell Cycle Proteins
  • Membrane Transport Proteins
  • OPTN protein, human
  • Transcription Factor TFIIIA