Abstract
Purpose To study the roles of sequence alterations in the optineurin (OPTN) gene-coding region in normal-tension glaucoma (NTG) among Chinese patients. Methods Genomic DNA was extracted from 190 NTG patients and 201 control subjects. The thirteen exons of OPTN were amplified by polymerase chain reaction and analyzed by direct sequencing. Detected sequence changes were compared between NTG patients and control subjects. Results Seven sequence changes in OPTN were identified in both NTG patients and control subjects. Among them, c.464G>A (T34 T), c.509C>T (T49T), c.806G>A (V148V), and c.959T>C (P199P) were synonymous codon changes, whilst c.655T>A (M98K), c.1996G>A (R545Q), and c.1582T>C (I407T) were missense changes. Two previously reported heterozygous mutations, c.458G>A (E50K) in exon 4 and c.691_692insAG in exon 6, were not found in this study. Out of these seven OPTN sequence variants, c.464G>A (T34T) was significantly associated with NTG in both the allelic and genotypic association analyses (allelic association: p = 0.0001, OR = 2.20, 95% CI: 1.46-3.31; genotypic association: p = 0.0001), whereas the association of other variants with NTG did not reach statistical significance (p > 0.05). Variants c.1582 T>C (I407T) and c.806G>A (V148V) were identified in one and two NTG patients, respectively, but not in the control subjects. Conclusions This study confirmed the association of the OPTN T34T variant with NTG, suggesting that OPTN is a susceptibility gene for NTG in Chinese. Moreover, a variant with amino acid change (I407T) was identified in NTG but not in controls. Further studies are warranted to assess whether this variant is a causative mutation for NTG.
Highlights
Glaucoma, a leading cause of irreversible blindness worldwide [1], is a heterogeneous group of optic neuropathies characterized by progressive degeneration of the optic nerve, and it could be detected clinically as cupping of the nerve head, thinning of the retinal nerve fiber layer, and typical visual field defect [2]
According to the morphology of the anterior chamber angle, primary glaucoma can be classified into primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG)
We found c.655T>A (M98K), c.1996G>A (R545Q), c.464G>A (T34T), c.509C>T (T49T), and c. 959T>C (P199P) in both normal-tension glaucoma (NTG) patients and control subjects
Summary
A leading cause of irreversible blindness worldwide [1], is a heterogeneous group of optic neuropathies characterized by progressive degeneration of the optic nerve, and it could be detected clinically as cupping of the nerve head, thinning of the retinal nerve fiber layer, and typical visual field defect [2]. Previous studies have reported gene mutations in NTG patients, like endothelin-1 (EDN1), optic atrophy type. In 2002, Rezaie et al identified OPTN mutations that were responsible for some of the hereditary NTGs [5]. Four mutations in OPTN, c.458G>A (E50K), c.655T>A (M98K), c.1996G>A (R545Q), and c.691_692insAG (2 bp “AG” insertion) were detected from 54 families with adult-onset POAG in which most families displayed normal IOP [5]. One of the rare mutations, E50K, showed a strong association with POAG, with NTG [6]. Disease Markers mutations and genetic association with NTG in Asians.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
