Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma
Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma
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DOI：
10.1016/s0002-9394(03)00577-4
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发表时间：
2003-11-01
影响因子：
4.2
通讯作者：
Stone, EM
中科院分区：
文献类型：
--
作者：
Alward, WLM;Kwon, YH;Stone, EM
目的：探讨optineurin（OPTN）基因的序列变异在开放性，角型glaucoma.Design：前瞻性病例对照study.Methods：OPTN基因的序列变异进行了筛选，使用单链构象多态性分析和自动DNA测序相结合。总共有1,299名受试者（1048名青光眼患者和251名对照）被筛选出先前与青光眼相关的基因的四个部分的变异。对这些受试者的一个子集（376例患者和176例对照）进行了整个编码序列变异的筛查。24%的患者和35%的对照组是日本人，而其余的主要是白人。等位基因频率进行了比较与Fisher精确test.Results：OPTN序列的变化是没有显着相关的任何形式的高眼压性开角型青光眼。一个家族正常的先证者，眼压性青光眼被发现窝藏先前报道的GIu 50 Lys变异。另一个先前报道的变化，Met 98赖氨酸，与正常眼压青光眼在日本，但不是在高加索patients.Conclusions：这项研究提供了一些额外的证据，与家族性正常眼压青光眼的关联Glu 50 Lys OPTN序列变异。然而，由于家族性正常眼压性青光眼是如此罕见，这种变化似乎是负责所有开角型青光眼不到0.1%。Arg 545 Gln变异可能是一种非致病性多态性。Met 98 Lys的变化可能与日本种族患者的正常眼压性青光眼有关。
Purpose: To investigate the association of sequence variations in the optineurin (OPTN) gene in patients with open,angle glaucoma.Design: Prospective case control study.Methods: The OPTN gene was screened for sequence variations using a combination of single-strand conformational polymorphism analysis and automated DNA sequencing. A total of 1,299 subjects (1048 glaucoma patients and 251 controls) were screened for variations in the four portions of the gene that had been previously associated with glaucoma. A subset of these subjects (376 patients and 176 controls) was screened for variations in the entire coding sequence. Twenty-four percent of the patients and 35% of the controls were Japanese, whereas the remainder were predominantly Caucasian. Allele frequencies were compared with the Fisher exact test.Results: The OPTN sequence variations were not significantly associated with any form of high-tension open-angle glaucoma. One proband with familial normal, tension glaucoma was found to harbor the previously reported GIu50Lys variation. Another previously reported change, Met98Lys, was associated with normal-tension glaucoma in Japanese but not in Caucasian patients.Conclusions: This study provides some additional evidence for the association of the Glu50Lys OPTN sequence variation with familial normal tension glaucoma. However, because familial normal-tension glaucoma is so rare, this change seems to be responsible for less than 0.1% of all open-angle glaucoma. The Arg545Gln variation is likely to be a nondisease-causing polymorphism. The Met98Lys change may be associated with a fraction of normal-tension glaucoma in patients of Japanese ethnicity.