Variants in optineurin gene and their association with tumor necrosis factor-α polymorphisms in Japanese patients with glaucoma
Variants in optineurin gene and their association with tumor necrosis factor-α polymorphisms in Japanese patients with glaucoma
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DOI：
10.1167/iovs.03-1403
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
Mashima, Y
中科院分区：
文献类型：
--
作者：
Funayama, T;Ishikawa, K;Mashima, Y
目的.研究日本人原发性恶性肿瘤患者视神经磷酸酶（OPTN）基因序列变异及其与TNF-α多态性的关系。在629名日本受试者的血液样本中分析了OPTN基因。有194例原发性开角型青光眼（POAG），217例正常眼压性青光眼（NTG），218例无眼病（对照组）。通过变性高效液相色谱法筛选基因突变。对TNF-α启动子区-308G->A、-857C->T和-863C->A三种多态性进行基因分型。分析各基因型与年龄、眼内压（IOP）和诊断时视野缺损的关系。在411例日本青光眼患者中发现了1例可能导致青光眼的突变His 26 Asp。OPTN基因c.412G-->A（Thr 34 Thr）多态性与POAG显著相关（基因型频率，P=0.011;等位基因频率，P=0.003）。POAG患者TNF-α/-857T和optineurin/412 A携带者的频率显著高于对照组（P=0.006）。在携带TNF-α/-857T的POAG患者中，optineurin/412 A携带者的视野评分显著低于非optineurin/412 A携带者（P=0.020）。POAG（P=0.008）或NTG（P =0.027）患者TNF-α/-863A和optineurin/603 A（或Lys 98）携带者的频率显著高于对照组。在携带TNF-α/-863A的POAG患者中，optineurin/603 A（或Lys 98）携带者的视野评分显著低于非optineurin/603 A（或Lys 98）携带者（P=0.026）。这些结果表明，OPTN基因与POAG而不是NTG在日本。统计分析显示OPTN和TNF-α基因多态性之间可能存在相互作用，这将增加青光眼的风险。
Purpose. To investigate sequence variations in the optineurin (OPTN) gene and their association with TNF-alpha 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-alpha 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-alpha/-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-alpha/-857T, the optineurin/412A carriers had significantly worse (P=0.020) visual field scores than the non-optineurin/412A ones. The frequency of TNF-alpha/-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-alpha/-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-alpha genes that would increase the risk for glaucoma.