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

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.