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OPA1 increases the risk of normal but not high tension glaucoma

OPA1 increases the risk of normal but not high tension glaucoma
OPA1 increases the risk of normal but not high tension glaucoma
Background
Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological optic disc cupping and visual field defects. The OPA1 gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic mutations cause autosomal dominant optic atrophy by specifically targeting retinal ganglion cells. This raises the distinct possibility that more subtle genetic variations in OPA1 could alter the risk of developing glaucoma.

Methods
137 patients with primary open angle glaucoma (67 patients with high-tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75 controls from the North East of England were studied. Three single-nucleotide polymorphisms in intron 8 (IVS8+4c/t and IVS8+32t/c) and exon 4 (c.473A/G) of the OPA1 gene were genotyped in the
study group. In addition, the entire OPA1 coding region
was sequenced in 24 individuals with the CT/TT
compound genotype using standard BigDye chemistries.

Results
There was no difference in either allele or genotype frequency for the IVS8+32t/c singlenucleotide polymorphisms between patients and controls, but there was a significant association between the T allele at IVS8+4c/t and the risk of developing NTG (OR¼2.04, 95% CI¼1.10 to 3.81, p¼0.004), but not HTG. Logistic regression analysis also confirmed a strong association between the CT/TT compound genotype at
IVS8+4 and IVS8+32 with NTG (OR¼29.75, 95% CI¼3.83 to 231.21, p¼0.001).

Conclusions
The CT/TT compound genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but not HTG.
0022-2593
120-125
Yu-Wai-Man, P.
ed57f03a-3af0-415d-8c7c-f6685e67c00f
Stewart, J .D.
e1ec9784-39cc-48ed-9f4f-2a05d25f2106
Hudson, G.
27591c21-a00b-4dff-bea1-744c66e07e52
Andrews, R. M.
5959ea86-04b7-45ca-b340-2f3854363319
Griffiths, P. G.
d846f6b7-abe2-465a-920a-aa9b4b86c1f0
Birch, M. K.
34593a2b-3145-4ee5-8893-354d0ad42687
Chinnery, P. F.
251d39a2-98fd-406f-9d33-24821f1b74b7
Yu-Wai-Man, P.
ed57f03a-3af0-415d-8c7c-f6685e67c00f
Stewart, J .D.
e1ec9784-39cc-48ed-9f4f-2a05d25f2106
Hudson, G.
27591c21-a00b-4dff-bea1-744c66e07e52
Andrews, R. M.
5959ea86-04b7-45ca-b340-2f3854363319
Griffiths, P. G.
d846f6b7-abe2-465a-920a-aa9b4b86c1f0
Birch, M. K.
34593a2b-3145-4ee5-8893-354d0ad42687
Chinnery, P. F.
251d39a2-98fd-406f-9d33-24821f1b74b7

Yu-Wai-Man, P., Stewart, J .D., Hudson, G., Andrews, R. M., Griffiths, P. G., Birch, M. K. and Chinnery, P. F. (2010) OPA1 increases the risk of normal but not high tension glaucoma. Journal of Medical Genetics, 47 (2), 120-125. (doi:10.1136/jmg.2009.067512). (PMID:19581274)

Record type: Article

Abstract

Background
Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological optic disc cupping and visual field defects. The OPA1 gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic mutations cause autosomal dominant optic atrophy by specifically targeting retinal ganglion cells. This raises the distinct possibility that more subtle genetic variations in OPA1 could alter the risk of developing glaucoma.

Methods
137 patients with primary open angle glaucoma (67 patients with high-tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75 controls from the North East of England were studied. Three single-nucleotide polymorphisms in intron 8 (IVS8+4c/t and IVS8+32t/c) and exon 4 (c.473A/G) of the OPA1 gene were genotyped in the
study group. In addition, the entire OPA1 coding region
was sequenced in 24 individuals with the CT/TT
compound genotype using standard BigDye chemistries.

Results
There was no difference in either allele or genotype frequency for the IVS8+32t/c singlenucleotide polymorphisms between patients and controls, but there was a significant association between the T allele at IVS8+4c/t and the risk of developing NTG (OR¼2.04, 95% CI¼1.10 to 3.81, p¼0.004), but not HTG. Logistic regression analysis also confirmed a strong association between the CT/TT compound genotype at
IVS8+4 and IVS8+32 with NTG (OR¼29.75, 95% CI¼3.83 to 231.21, p¼0.001).

Conclusions
The CT/TT compound genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but not HTG.

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Published date: February 2010
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 355911
URI: http://eprints.soton.ac.uk/id/eprint/355911
ISSN: 0022-2593
PURE UUID: 696fae8d-686c-43c0-be0a-51486dd78f6d
ORCID for J .D. Stewart: ORCID iD orcid.org/0000-0002-2608-1967

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Date deposited: 04 Sep 2013 16:57
Last modified: 14 Sep 2021 17:25

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Contributors

Author: P. Yu-Wai-Man
Author: J .D. Stewart ORCID iD
Author: G. Hudson
Author: R. M. Andrews
Author: P. G. Griffiths
Author: M. K. Birch
Author: P. F. Chinnery

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