The OPA1 gene polymorphism is associated with normal tension and high tension glaucoma.
OBJECTIVE
To assess whether genetic polymorphisms of optic atrophy 1 (OPA1) are associated with primary open-angle glaucoma (POAG).


METHODS
Prospective case control association study.


METHODS
Japanese patients with normal tension glaucoma (NTG, n = 194), and high tension glaucoma (HTG, n = 191), and 185 control subjects were analyzed for the OPA1 intervening sequence (IVS) 8+4 cystosine thymine (C/T) and IVS 8+32 thymine cystosine (T/C) polymorphisms using pyrosequencing technique.


RESULTS
There was a significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the NTG patients and control subjects (P = .0074), and the frequency of the cystosine (C) allele was significantly higher in the NTG patients compared with the control subjects (19.3% vs 11.6%, P = .0036). Adjusted for age, gender, refractive error, and intraocular pressure, an almost two-fold increased risk of NTG (P = .004, odds ratio 2.27, 95% confidence interval 1.30 to 3.97) was found with the OPA1 IVS 8 +32 C allele. Although there was no significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the HTG patients and control subjects (P = .24), the age at the time of diagnosis (53 +/- 11.0 years, median value +/- median absolute deviation) in the HTG patients with the OPA1 IVS 8 +32 C allele was significantly younger than that (57 +/- 12.0 years) in the HTG patients without C allele (P = .048).


CONCLUSIONS
The OPA1 IVS 8 +32 T/C polymorphism is associated with NTG, and may be used as a marker for this disease association. This polymorphism also influences the phenotypic feature in patients with HTG and should be considered to be a genetic risk factor not only for NTG, but also for HTG.
Mabuchi
Fumihiko
F
Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. fmabushi@yamanashi.ac.jp
Tang
Sa
S
Kashiwagi
Kenji
K
Yamagata
Zentaro
Z
Iijima
Hiroyuki
H
Tsukahara
Shigeo
S
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000235:genetics; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors
D005819:Genetic Markers; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human