The role of the Met98Lys optineurin variant in inherited optic nerve diseases.

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.

• Authors: J E Craig, A W Hewitt, D P Dimasi, N Howell, C Toomes, A C Cohn, D A Mackey
• Journal: The British journal of ophthalmology (Br J Ophthalmol) Vol. 90 Issue 11 Pg. 1420-4 (Nov 2006) ISSN: 0007-1161 [Print] England
• PMID: 16885188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adolescent
• Adult
• Alleles
• Case-Control Studies
• Cell Cycle Proteins
• Chi-Square Distribution
• Child
• DNA Mutational Analysis
• DNA, Mitochondrial (genetics)
• Female
• Gene Frequency
• Glaucoma, Open-Angle (genetics)
• Heterozygote
• Humans
• Male
• Membrane Transport Proteins
• Mutation
• Optic Atrophy, Autosomal Dominant (genetics)
• Optic Atrophy, Hereditary, Leber (genetics)
• Optic Nerve Diseases (genetics)
• Pedigree
• Transcription Factor TFIIIA (genetics)