Screening for mutations of the HFE gene in Parkinson's disease patients with hyperechogenicity of the substantia nigra
Screening for mutations of the HFE gene in Parkinson's disease patients with hyperechogenicity of the substantia nigra
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DOI：
10.1016/j.neulet.2006.07.070
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发表时间：
2006-10-16
影响因子：
2.5
通讯作者：
Berg, Daniela
中科院分区：
文献类型：
--
作者：
Akbas, Nilguen;Hochstrasser, Helmine;Berg, Daniela
已知铁介导的氧化应激会导致帕金森病 (PD) 的神经退行性过程。尽管有迹象表明，在某些情况下，参与脑铁代谢的基因可能参与帕金森病的发病机制，但仍不清楚脑铁含量的增加是否构成疾病级联中的主要或次要事件。最近关于血色素沉着病基因 (HFE) 突变在 PD 中的作用的研究各不相同，从 C282Y 杂合性的保护作用、C282Y 或 H63D 突变没有影响到 C282Y 突变携带者患 PD 的风险增加。在这项研究中，通过 dHPLC 分析了 278 名 PD 患者的 HFE 基因的整个编码区，之前通过经颅超声检查发现黑质 (SN) 铁含量增加，我们没有发现常见的 HFE 突变与 PD 之间的关联。然而，我们在一名 PD 患者中发现了两种新的变异（K92N 和 1217T）。在任何对照中均未发现这些变化。未来的研究有必要揭示这些突变与 PD 可能的功能相关性。我们的结果表明，HFE 基因突变并不是导致 SN 铁水平升高的 PD 的常见原因。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
Iron mediated oxidative stress is known to contribute to the neurodegenerative process in Parkinson's disease (PD). Although there are hints that genes involved in brain iron metabolism might be involved in the pathogenesis of PD in some instances, it is still not known whether the increase in brain iron content constitutes a primary or secondary event in the disease cascade. Recent studies on the role of hemochromatosis gene (HFE) mutations in PD vary from a protective effect of C282Y heterozygosity, no effect of the C282Y or H63D mutation to an increased risk for PD in C282Y mutation carriers. In this study, analyzing the whole coding region of the HFE gene by dHPLC in 278 PD patients, priorly characterized by transcranial sonography for increased iron content of the substantia nigra (SN), we did not find an association of the common HFE mutations and PD. However, we identified two novel variants (K92N and 1217T) each in a single PD patient. These variations were not found in any of the controls. Future studies are necessary to reveal a possible functional relevance of these mutations for PD. Our results indicate that mutations in the HFE gene are not a common cause for PD with increased iron levels of the SN. (c) 2006 Elsevier Ireland Ltd. All rights reserved.