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The role of the Met98Lys optineurin variant in inherited optic nerve diseases
  1. J E Craig1,
  2. A W Hewitt1,2,
  3. D P Dimasi1,
  4. N Howell3,
  5. C Toomes4,
  6. A C Cohn2,
  7. D A Mackey2,5
  1. 1Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia
  2. 2Clinical Genetics Unit, Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
  3. 3MIGENIX Corporation, San Diego, California, USA
  4. 4Section of Ophthalmology and Neuroscience, University of Leeds, Leeds, UK
  5. 5Department of Ophthalmology, University of Tasmania, Royal Hobart Hospital, Hobart, Tasmania, Australia
  1. Correspondence to: J Craig Department of Ophthalmology, Flinders University, Flinders Drive, Bedford Park, South Australia 5042, Australia;jamie.craig{at}flinders.edu.au

Abstract

Aims: To investigate the role of the common OPTN Met98Lys variant as a risk allele in open-angle glaucoma (OAG), autosomal dominant optic atrophy (ADOA) and Leber’s hereditary optic neuropathy (LHON).

Methods: The presence of the Met98Lys variant was determined in a total of 498 (128 with normal-tension glaucoma (NTG)) patients with OAG, 29 patients who had myocilin-related OAG, 101 patients from ADOA pedigrees, 157 patients from LHON pedigrees and 218 examined OAG age-matched normal controls.

Results: 17 of 218 (7.8%) controls had the Met98Lys variant. 28 (5.6%) patients with OAG were Met98Lys positive. More Met98Lys carriers were found in the NTG group than in the high-tension glaucoma (HTG) group (p = 0.033). However, no significant difference was observed between the NTG and control cohorts (p = 0.609). Two MYOC mutation carriers were found to have the variant. The variant was found in 1 of 10 pedigrees with ADOA and in 8 of 35 pedigrees with LHON.

Conclusion: Data from this study do not support a strong role for the OPTN Met98Lys variant in glaucoma, ADOA or LHON. However, a weak association was observed of the variant with NTG compared with that with HTG. Meta-analysis of all published data on the variant and glaucoma confirmed that the association, although weak, is highly statistically significant in the cohort with glaucoma versus controls.

  • ADOA, autosomal dominant optic atrophy
  • GIST, Glaucoma Inheritance Study in Tasmania
  • HTG, high-tension glaucoma
  • IOP, intraocular pressure
  • LHON, Leber’s hereditary optic neuropathy
  • mtDNA, mitochondrial DNA
  • NTG, normal-tension glaucoma
  • OAG, open-angle glaucoma
  • POAG, primary open-angle glaucoma

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Footnotes

  • Published Online First 2 August 2006

  • Funding: This research was supported by the NH&MRC Project Grant number 229960, the Jack Brockhoff Foundation, the Ophthalmic Research Institute of Australia and Glaucoma Australia. JEC is supported in part by an NHMRC Practitioner Fellowship. AWH is supported by a NHMRC Medical Postgraduate Scholarship and CT is a Royal Society University Research Fellow.

  • Competing interests: None.

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