Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma

Am J Ophthalmol. 2003 Nov;136(5):904-10. doi: 10.1016/s0002-9394(03)00577-4.


Purpose: To investigate the association of sequence variations in the optineurin (OPTN) gene in patients with open-angle glaucoma.

Design: Prospective case control study.

Methods: The OPTN gene was screened for sequence variations using a combination of single-strand conformational polymorphism analysis and automated DNA sequencing. A total of 1,299 subjects (1048 glaucoma patients and 251 controls) were screened for variations in the four portions of the gene that had been previously associated with glaucoma. A subset of these subjects (376 patients and 176 controls) was screened for variations in the entire coding sequence. Twenty-four percent of the patients and 35% of the controls were Japanese, whereas the remainder were predominantly Caucasian. Allele frequencies were compared with the Fisher exact test.

Results: The OPTN sequence variations were not significantly associated with any form of high-tension open-angle glaucoma. One proband with familial normal-tension glaucoma was found to harbor the previously reported Glu50Lys variation. Another previously reported change, Met98Lys, was associated with normal-tension glaucoma in Japanese but not in Caucasian patients.

Conclusions: This study provides some additional evidence for the association of the Glu50Lys OPTN sequence variation with familial normal tension glaucoma. However, because familial normal-tension glaucoma is so rare, this change seems to be responsible for less than 0.1% of all open-angle glaucoma. The Arg545Gln variation is likely to be a nondisease-causing polymorphism. The Met98Lys change may be associated with a fraction of normal-tension glaucoma in patients of Japanese ethnicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Case-Control Studies
  • Cell Cycle Proteins
  • DNA Primers / chemistry
  • Eye Proteins / genetics*
  • Female
  • Glaucoma, Open-Angle / genetics*
  • Humans
  • Membrane Transport Proteins
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Prospective Studies
  • Sequence Analysis, DNA
  • Transcription Factor TFIIIA*


  • Cell Cycle Proteins
  • DNA Primers
  • Eye Proteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • OPTN protein, human
  • Transcription Factor TFIIIA