Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma.
OBJECTIVE
To investigate the association of sequence variations in the optineurin (OPTN) gene in patients with open-angle glaucoma.


METHODS
Prospective case control study.


METHODS
The OPTN gene was screened for sequence variations using a combination of single-strand conformational polymorphism analysis and automated DNA sequencing. A total of 1,299 subjects (1048 glaucoma patients and 251 controls) were screened for variations in the four portions of the gene that had been previously associated with glaucoma. A subset of these subjects (376 patients and 176 controls) was screened for variations in the entire coding sequence. Twenty-four percent of the patients and 35% of the controls were Japanese, whereas the remainder were predominantly Caucasian. Allele frequencies were compared with the Fisher exact test.


RESULTS
The OPTN sequence variations were not significantly associated with any form of high-tension open-angle glaucoma. One proband with familial normal-tension glaucoma was found to harbor the previously reported Glu50Lys variation. Another previously reported change, Met98Lys, was associated with normal-tension glaucoma in Japanese but not in Caucasian patients.


CONCLUSIONS
This study provides some additional evidence for the association of the Glu50Lys OPTN sequence variation with familial normal tension glaucoma. However, because familial normal-tension glaucoma is so rare, this change seems to be responsible for less than 0.1% of all open-angle glaucoma. The Arg545Gln variation is likely to be a nondisease-causing polymorphism. The Met98Lys change may be associated with a fraction of normal-tension glaucoma in patients of Japanese ethnicity.
Alward
Wallace L M
WL
Department of Ophthalmology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
Kwon
Young H
YH
Kawase
Kazuhide
K
Craig
Jamie E
JE
Hayreh
Sohan S
SS
Johnson
A Tim
AT
Khanna
Cheryl L
CL
Yamamoto
Tetsuya
T
Mackey
David A
DA
Roos
Benjamin R
BR
Affatigato
Louisa M
LM
Sheffield
Val C
VC
Stone
Edwin M
EM
D001483:Base Sequence; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D017931:DNA Primers / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D035582:Transcription Factor TFIIIA
D018797:Cell Cycle Proteins; D017931:DNA Primers; D005136:Eye Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA