Original article
The OPA1 Gene Polymorphism is Associated With Normal Tension and High Tension Glaucoma

https://doi.org/10.1016/j.ajo.2006.09.028Get rights and content

Purpose

To assess whether genetic polymorphisms of optic atrophy 1 (OPA1) are associated with primary open-angle glaucoma (POAG).

Design

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.

Section snippets

Subjects

Japanese patients with POAG were recruited from ophthalmology practices in the University of Yamanashi Hospital, Enzan City Hospital, Uenohara Town Hospital, and Oizumi Clinic in Yamanashi or Nagano prefectures, Japan. Diagnosis of POAG required open angles on gonioscopic examination, typical glaucomatous cupping of the optic disk with compatible visual field defects by automated static perimetry (Humphrey Visual Field Analyzer 30-2, Humphrey Instruments, San Leandro, California, USA).

Results

One hundred and ninety-four Japanese patients with NTG, 191 patients with HTG, and 185 control subjects were enrolled in this study. The mean age at the time of blood sampling was 63.6 ± 13.3 years standard deviation (SD) in patients with NTG, 62.3 ± 15.1 years in patients with HTG, and 65.3 ± 11.5 years in the control subjects. The mean age at the time of diagnosis was 57.5 ± 13.3 and 54.1 ± 15.6 years in patients with NTG and HTG, respectively. The mean and standard deviation of maximum known

Discussion

Mitochondria are important participants in apoptosis, releasing cytochrome C into the cytoplasm and undergoing extensive mitochondrial fragmentation. The OPA1 gene encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the formation and maintenance of the mitochondrial network and morphology. It was suggested that an initial mitochondrial leak of OPA1 might lead to cristae structural alterations and exposure of previously sequestered protein pools, permitting continued

Fumihiko Mabuchi, MD, PhD, is an instructor of the Department of Ophthalmology at the University of Yamanashi in Yamanashi, Japan. He received his MD and PhD from Yamanashi Medical University in 1993 and 2001, respectively, and then undertook experimental research as an international fellow at Hamilton Glaucoma Center, University of California, San Diego from 2001 to 2003. Dr Mabuchi clinical expertise is diagnosis and management of glaucoma, and current research interests include genetics of

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Fumihiko Mabuchi, MD, PhD, is an instructor of the Department of Ophthalmology at the University of Yamanashi in Yamanashi, Japan. He received his MD and PhD from Yamanashi Medical University in 1993 and 2001, respectively, and then undertook experimental research as an international fellow at Hamilton Glaucoma Center, University of California, San Diego from 2001 to 2003. Dr Mabuchi clinical expertise is diagnosis and management of glaucoma, and current research interests include genetics of primary open-angle glaucoma.

Hiroyuki Iijima, MD, PhD, is a Professor and Chairman of Ophthalmology at the University of Yamanashi since 1999. He earned his medical degree from Tokyo University in 1978 and completed a fellowship in Ophthalmology at Tokyo University. Dr Iijima joined the faculty at Yamanashi, Medical College, the predecessor of the present University of Yamanashi, in 1982. Dr Iijima’s research interests include clinical perimetry, fundus imaging, laser treatment, and genetics in the field of medical retina.

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