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


CONCLUSIONS
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.
Craig
J E
JE
Department of Ophthalmology, Flinders University, Flinders Drive, Bedford Park, South Australia 5042, Australia. jamie.craig@flinders.edu.au
Hewitt
A W
AW
Dimasi
D P
DP
Howell
N
N
Toomes
C
C
Cohn
A C
AC
Mackey
D A
DA
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D016009:Chi-Square Distribution; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics; D009901:Optic Nerve Diseases / Q000235:genetics*; D010375:Pedigree; D035582:Transcription Factor TFIIIA / Q000235:genetics*
D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA