中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (33): 3116-3123.doi: 10.3969/j.issn.1673-5374.2013.33.005

• 原著:退行性病与再生 • 上一篇    下一篇

微管相关蛋白Tau基因是中国汉族人群肌萎缩侧索硬化症的易感基因？

  

  • 收稿日期:2013-07-03 修回日期:2013-09-15 出版日期:2013-11-25 发布日期:2013-11-25

MAPT as a predisposing gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population

Pu Fang, Wenyuan Xu, Chengsi Wu, Min Zhu, Xiaobing Li, Daojun Hong   

  1. Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
  • Received:2013-07-03 Revised:2013-09-15 Online:2013-11-25 Published:2013-11-25
  • Contact: Daojun Hong, M.D., Ph.D., Associate chief physician, Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China, daojunhong@yahoo.com.cn; fangpu1972@163.com.
  • About author:Pu Fang, Master, Chief physician. Pu Fang and Wenyuan Xu contributed equally to this article.

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摘要：

一项纳入416 例欧洲白种人散发性肌萎缩性脊髓侧索硬化症患者和242名对照者的以往研究中发现微管相关蛋白Tau基因二核苷酸多态性与散发性肌萎缩性脊髓侧索硬化症的发病存在显著的相关性。为了进一步确定微管相关蛋白Tau基因与中国汉族人群散发性肌萎缩性脊髓侧索硬化症患者存在可能潜在相关性，研究招募107例中国汉族人群的散发性肌萎缩性脊髓侧索硬化症患者和100名健康对照者。采用直接扩增测序的方法，对患者外周血微管相关蛋白Tau基因3'和5'非翻译区，以及内含子9，10，11和12的碱基变异进行检查。结果发现，共有33个微管相关蛋白Tau基因的遗传变异位点被发现证实。其中，第9内含子105788 A > G变异显示：散发性肌萎缩性脊髓侧索硬化症患者A和G等位基因频率分别为92.06％和7.94％; 第11号内含子123972 T>A 变异显示：散发性肌萎缩性脊髓侧索硬化症患者T和A等位基因频率分别为92.99％和7.01％，以上指标与健康对照组相比差异均有显著性意义。进一步对对象的临床资料分析显示，携带微管相关蛋白Tau基因105788 A > G和123972 T > A 变异的散发性肌萎缩性脊髓侧索硬化症患者，发病年龄较无微管相关蛋白Tau基因的遗传变异的患者年轻。此外，有微管相关蛋白Tau基因变异的患者更容易出现延髓麻痹和呼吸困难，最终导致存在微管相关蛋白Tau基因的遗传变异患者的生存期更短。证实微管相关蛋白Tau基因可能是中国汉族人群的散发性肌萎缩性脊髓侧索硬化症的一种发病易感基因。

关键词: 神经再生, 临床实践, 神经退行性变, 散发性肌萎缩侧索硬化症, 肌萎缩侧索硬化症, 微管相关蛋白Tau基因, 中国汉族人群, 基因型, 等位基因频率, 年龄, 易感基因

Abstract:

A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau (MAPT) gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population. We screened the mutation-susceptible regions of MAPT – the 3′ and 5′ untranslated regions as well as introns 9, 10, 11, and 12 – by direct sequencing, and identified 33 genetic variations. Two of these, 105788 A > G in intron 9 and 123972 T > A in intron 11, were not present in the control group. The age of onset in patients with the 105788 A > G and/or the 123972 T > A variant was younger than that in patients without either genetic variation. Moreover, the pa-tients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.

Key words: neural regeneration, sporadic amyotrophic lateral sclerosis, microtubule-associated protein Tau gene, MAPT, Chinese Han population, genotype, neuroregeneration