Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients

Tomoko Umeda, Toshihiko Matsuo, Mikio Nagayama, Naoyuki Tamura, Yuko Tanabe, Hiroshi Ohtsuki

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Purpose: To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Methods: Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. Results: The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p = 0-0147) and NTG (4/28, 14.2%, p = 0-0369) patients, and even in both the POAG and NTG patients combined (12/83, 14-4%, p = 0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G > A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G > A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C > T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G > A showed significantly larger cup-to-disc ratios (p = 0-0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p = 0.0076), and a significantly higher rate of surgery and/or laser history (p = 0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. Conclusions: Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G > A, may be a genetic risk factor for the progression of open-angle glaucoma in this Japanese population.

Original languageEnglish
Pages (from-to)91-99
Number of pages9
JournalOphthalmic Genetics
Issue number2
Publication statusPublished - Jun 2004


  • Genetics
  • Glaucoma
  • Optineurin
  • Polymorphism
  • Trabeculectomy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Ophthalmology
  • Genetics(clinical)


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