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Tomoyo Funayama, Karin Ishikawa, Yuichiro Ohtake, Tomihiko Tanino, Daijiro Kurosaka, Itaru Kimura, Kotaro Suzuki, Hidenao Ideta, Kenji Nakamoto, Noriko Yasuda, Takuro Fujimaki, Akira Murakami, Ryo Asaoka, Yoshihiro Hotta, Hidenobu Tanihara, Takashi Kanamoto, Hiromu Mishima, Takeo Fukuchi, Haruki Abe, Takeshi Iwata, Naoki Shimada, Jun Kudoh, Nobuyoshi Shimizu, Yukihiko Mashima; Variants in Optineurin Gene and Their Association with Tumor Necrosis Factor-α Polymorphisms in Japanese Patients with Glaucoma. Invest. Ophthalmol. Vis. Sci. 2004;45(12):4359-4367. doi: https://doi.org/10.1167/iovs.03-1403.
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purpose. To investigate sequence variations in the optineurin (OPTN) gene and their association with TNF-α polymorphisms in Japanese patients with glaucoma.
methods. The OPTN gene was analyzed in blood samples from 629 Japanese subjects. There were 194 patients with primary open-angle glaucoma (POAG), 217 with normal-tension glaucoma (NTG), and 218 with no eye disease (control subjects). The gene was screened for mutations by denaturing high-performance liquid chromatography. Genotyping of three polymorphisms of −308G→A, −857C→T, and −863C→A in the TNF-α promoter region was performed. The associations between the genotypes and age, intraocular pressure (IOP), and visual field defects at the time of diagnosis were examined.
results. A possible glaucoma-causing mutation, His26Asp, was identified in 1 of the 411 Japanese patients with glaucoma. A c.412G→A (Thr34Thr) polymorphism in the OPTN gene was significantly associated with POAG (genotype frequency, P = 0.011; allele frequency, P = 0.003). The frequency of TNF-α/−857T and optineurin/412A carriers was significantly higher (P = 0.006) in patients with POAG than in control subjects. Among the patients with POAG who were carriers of TNF-α/−857T, the optineurin/412A carriers had significantly worse (P = 0.020) visual field scores than the non–optineurin/412A ones. The frequency of TNF-α/−863A and optineurin/603A (or Lys98) carriers was significantly higher in patients with POAG (P = 0.008) or NTG (P = 0.027) than in control subjects. Among the patients with POAG who were carriers of TNF-α/−863A, the ones with optineurin/603A (or Lys98) had significantly worse (P = 0.026) visual field scores than did those with non–optineurin/603A (or Lys98).
conclusions. These findings demonstrated that the OPTN gene is associated with POAG rather than NTG in the Japanese. Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-α genes that would increase the risk for glaucoma.
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