Research about etiology and prophylactic program in open angle glaucoma

开角型青光眼的病因及预防方案研究

• 批准号: 12670348
• 负责人: IIJIMA Hiroyuki
• 金额: $ 2.05万
• 依托单位: Yamanashi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670348/
• 关键词: Myocilin; MYOC; Primary Open Angle Glaucoma; Normal Tension Glaucoma; Genetic Analysis; PCR-SSCP; Mutation; Japanese; PCR-SSCP法

The myocilin gene was identified as a gene (MYOC) that caused open angle glaucoma. Single strand conformation polymorphism analysis and subseauent sequence analysis were performed for genotyping the myocilin gene in 119 unrelated Japanese patients with primary open angle glaucoma (POAG), 114 patients withnormal tension glaucoma (NTG), and 100 control subjects without glaucoma. Nine sequence changes, including 5 amino acid sequence changes, were identified : Promotorl-83 G→A (10 POAG, four NTG, seven control), Arg46Stop (one NTG), Arg76Lys (10 POAG, fourNTG, seven control), Thrl23Thr (one POAG, one control), Argl58Gln (one POAG, one NTG, one control), Asp20.8Glu (three POAG, four NTG, one control), Pro481Ser (one control), Ala488Ala (one POAG, two control), 1515+20 G→A. (one NTG).Pro481Serwasnovel. Arg46Stopwas found inonly 1 patient withNTG in this study. However, the subjects without glaucoma, who were heterozygous or homozygous for Arg46Stop, were previously reported.Arg76Lys is cons … More idered to be a non-disease-causing polymorphism and always occurred with the 1-83 (G→A) in the promoter region. This haplotype may be specific to the Asian population. Argl58Gln is an only missense sequence change found in the leucine zipper-like motif region of the myocilin in subjects showing various phenotypes. Argl58Gln is probably a rare nondisease-causing polymorphism, because it was found in a control subject, although Argl58Gln Was previously reported as a probable disease-causing mutation. When the patients with open angle glaucoma were compared with control subjects, there was a trend toward an association of Asp208Glu with the presence of glaucoma.Interestingly, the combination of Asp208Glu and Pro481Serwas only found in a control. The interaction of Pro481Ser might have a protective effect. However, it was reported that Asp208Glu was found in five of 100 unrelated control subjects without glaucoma, which suggests that Arg208Glu is probably -a nondisease-causing polymorphism. Less

心肌蛋白基因是引起开角型青光眼的一个基因（MYOC）。对119例无亲缘关系的日本原发性开角型青光眼（POAG）患者、114例正常张力型青光眼（NTG）患者和100例无青光眼的对照患者进行了心肌蛋白基因单链构象多态性分析和后续序列分析。共鉴定出9个序列变化，包括5个氨基酸序列变化：Promotorl-83 G→A（10个POAG， 4个NTG， 7个对照）、Arg46Stop（1个NTG）、Arg76Lys（10个POAG， 4个NTG， 7个对照）、Thrl23Thr（1个POAG， 4个NTG， 7个对照）、Argl58Gln（1个POAG， 1个NTG， 1个对照）、Asp20.8Glu（3个POAG， 4个NTG， 1个对照）、Pro481Ser（1个对照）、Ala488Ala（1个POAG， 2个对照）、1515+20 G→A。(NTG) .Pro481Serwasnovel。本研究仅在1例ntg患者中发现arg46stop。然而，没有青光眼的受试者，无论是Arg46Stop的杂合型还是纯合型，之前都有报道。Arg76Lys被认为是一种非致病多态性，常发生在启动子区1-83 （G→a）位点。这种单倍型可能是亚洲人特有的。Argl58Gln是在不同表型的受试者中发现的唯一在肌鞘亮氨酸拉链样基序区域的错义序列变化。Argl58Gln可能是一种罕见的非致病多态性，因为它是在对照受试者中发现的，尽管Argl58Gln之前被报道为可能的致病突变。当开角型青光眼患者与对照组比较时，Asp208Glu与青光眼的存在有关联的趋势。有趣的是，Asp208Glu和pro481seru的组合仅在对照中被发现。Pro481Ser的相互作用可能具有保护作用。然而，据报道，在100名无青光眼的对照受试者中，有5人发现了Asp208Glu，这表明Arg208Glu可能是一种非致病多态性。少

项目成果

Fumihiko Mabuchi: "Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open angle glaucoma"Clinical Geneties. 59 (4). 263-268 (2001)

Fumihiko Mabuchi：“日本正常眼压性青光眼和原发性开角型青光眼患者肌纤蛋白基因突变分析”临床遗传学。

Fumihiko Mabuchi: "A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein"Journal of Human Genetics. 46(2). 85-89 (2001)

Fumihiko Mabuchi：“MYOC/TIGR 蛋白亮氨酸拉链样基序区域的序列变化 (Arg158Gln)”人类遗传学杂志。

Fumihiko Mabuchi: "Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open angle glaucoma"Clinical Genetics. 59(4). 263-268 (2001)

Fumihiko Mabuchi：“日本正常眼压性青光眼和原发性开角型青光眼患者肌纤蛋白基因突变分析”临床遗传学。

Fumihiko Mabuchi,Zentaro Yamagata,Kenji Kashiwagi,Kiyotaka Ishijima,Sa Tang,Hiroyuki Iijima,Shigeo Tsukahara: "A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein"Journal of Human Genetics. 46(2). 85-89 (2001)

Fumihiko Mabuchi、Zentaro Yamagata、Kenji Kashiwagi、Kiyotaka Ishijima、Sa Tang、Hiroyuki Iijima、Shigeo Tsukahara：“MYOC/TIGR 蛋白亮氨酸拉链样基序区域的序列变化 (Arg158Gln)”人类遗传学杂志。

Fumihiko Mabuchi,Zentaro Yamagata,Kenji Kashiwagi,Sa Tang,Hiroyuki Iijima,Shigeo Tsukahara: "Analysis of MYOC/TIGR gene mutations in Japanese patients with normal tension glaucoma and primary open angle glaucoma"Clinical Genetics. 59(in press). (2001)

Fumihiko Mabuchi、Zentaro Yamagata、Kenji Kashiwagi、Sa Tang、Hiroyuki Iijima、Shigeo Tsukahara：“日本正常眼压性青光眼和原发性开角型青光眼患者 MYOC/TIGR 基因突变分析”临床遗传学。