Restless Legs Syndrome-Associated MEIS1 Risk Variant Influences Iron Homeostasis
Restless Legs Syndrome-Associated MEIS1 Risk Variant Influences Iron Homeostasis
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DOI：
10.1002/ana.22435
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发表时间：
2011-07-01
影响因子：
11.2
通讯作者：
Rouleau, Guy A.
中科院分区：
文献类型：
--
作者：
Catoire, Helene;Dion, Patrick A.;Rouleau, Guy A.
不宁腿综合症(RLS)是一种常见的睡眠障碍，与铁稳态失调有关。遗传学研究证实Meis1是一种RLS易感基因，其中RLS风险单倍型与Meis1基因和蛋白表达降低有关。我们在这里表明，对Meis1蠕虫同源物的RNA干扰处理增加了线虫铁蛋白的表达，并且RLS相关的单倍型导致了RLS脑组织中铁蛋白和DMT1的表达增加。此外，在缺铁条件下培养的人类细胞显示Meis1的表达减少。我们的数据建立了RLS Meis1基因和铁代谢之间的联系。Ann Neurol 2011；70：170-175
Restless legs syndrome (RLS) is a frequent sleep disorder that is linked to disturbed iron homeostasis. Genetic studies identified MEIS1 as an RLS-predisposing gene, where the RLS risk haplotype is associated with decreased MEIS1 mRNA and protein expression. We show here that RNA interference treatment of the MEIS1 worm orthologue increases ferritin expression in Caenorhabditis elegans and that the RLS-associated haplotype leads to increased expression of ferritin and DMT1 in RLS brain tissues. Additionally, human cells cultured under iron-deficient conditions show reduced MEIS1 expression. Our data establish a link between the RLS MEIS1 gene and iron metabolism. ANN NEUROL 2011;70:170-175