Association between divalent metal transport 1 encoding gene (SLC11A2) and disease duration in amyotrophic lateral sclerosis
Association between divalent metal transport 1 encoding gene (SLC11A2) and disease duration in amyotrophic lateral sclerosis
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DOI：
10.1016/j.jns.2010.12.018
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发表时间：
2011-04-15
影响因子：
4.4
通讯作者：
Corcia, Philippe
中科院分区：
文献类型：
--
作者：
Blasco, Helene;Vourc'h, Patrick;Corcia, Philippe
背景：铁稳态失调是肌萎缩侧索硬化症（ALS）运动神经元变性的一种可能的病理生理机制。 SLC11A2 基因编码二价金属转运 1 (DMT1)，介导脑内体区室中的铁转运。本研究的目的是分析 DMT1 作为散发性 ALS (SALS) 的可能风险或调节因素。方法：我们对先前在另一种神经退行性疾病阿尔茨海默氏病中分析的内含子多态性 (rs407135) 进行了病例对照关联研究。通过对 579 名法国 SALS 患者和 517 名健康匹配个体进行 DNA 测序，研究了这种多态性。根据基因型分析患者的临床特征。结果：我们观察到，SLC11A2 中 rs407135 的 C 等位基因与腿部发病的 SALS 患者的病程较短相关[风险比：1.5 [1.1-2.1] (p = 0.02)]。这些结果与之前的观察结果一致，表明延髓和脊髓运动神经元具有不同的代谢调节和基因表达谱。结论：我们的研究结果支持 ALS 中铁代谢的含义，并表明 SLC11A2 基因的基因型可以调节法国 SALS 患者的疾病持续时间。 (C) 2010 Elsevier B.V. 保留所有权利。
Background: Dysregulation of iron homeostasis is one possible pathophysiological mechanism involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). SLC11A2 gene encodes the divalent metal transport 1 (DMT1) mediating iron transport in cerebral endosomal compartments. The objective of the study was to analyze DMT1 as a possible risk or modulating factor in sporadic ALS (SALS).Methods: We performed a case-control association study on an intronic polymorphism (rs407135) previously analyzed in another neurodegenerative disease, Alzheimer's disease. This polymorphism was studied by DNA sequencing in 579 French patients with SALS and 517 healthy matched individuals. The clinical characteristics of patients were analyzed in relation to their genotypes.Results: We observed that the C allele of rs407135 in SLC11A2 was associated with a shorter disease duration in SALS patients with onset in the legs [Hazard ratio: 1.5 [1.1-2.1] (p = 0.02)]. These results are in line with previous observations suggesting that bulbar and spinal motor neurons have different metabolic regulation and gene expression profiles.Conclusions: Our findings support an implication for iron metabolism in ALS and suggest that the genotype of the SLC11A2 gene could modulate the duration of the disease in French SALS patients. (C) 2010 Elsevier B.V. All rights reserved.