Functional association of the parkin gene promoter with idiopathic Parkinson's disease.
Functional association of the parkin gene promoter with idiopathic Parkinson's disease.
复制标题
Parkin 基因启动子与特发性帕金森病的功能关联。
DOI：
10.1093/hmg/11.22.2787
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发表时间：
2002
影响因子：
3.5
通讯作者：
Farrer,MattJ
中科院分区：
文献类型：
--
作者：
West,AndrewB;Maraganore,Demetrius;Crook,Julia;Lesnick,Tim;Lockhart,PaulJ;Wilkes,KristenM;Kapatos,Gregory;Hardy,JohnA;Farrer,MattJ
Parkinggene 的功能丧失突变首次在常染色体隐性遗传青少年帕金森病 (AR-JP) 中被发现。随后，在许多早发帕金森病（PD）患者（发病年龄<45岁）中发现了parkin突变。我们假设parkingene表达也可能导致与年龄相关的特发性PD风险（发病年龄>50岁）。已经鉴定并评估了parkincore启动子内的两个单核苷酸多态性。我们展示了其中一个变体 -258 T/G，位于 DNA 区域，该区域与来自人黑质体外的核蛋白结合，并在功能上影响基因转录。此外，根据大量基于人群的病例和对照系列的评估，-258 T/G 多态性在遗传上与特发性 PD 相关。我们的结果进一步表明parkinggene与帕金森病的发展有关。
Loss-of-function mutations in theparkingene were first identified in autosomal recessive juvenile parkinsonism (AR-JP). Subsequently,parkinmutations were found in many early-onset patients with Parkinson's disease (PD) (<45 years at onset). We hypothesized thatparkingene expression also may contribute to the age-associated risk of idiopathic PD (>50 years at onset). Two single-nucleotide polymorphisms within theparkincore promoter have been identified and assessed. We show one of the variants, −258 T/G, is located in a region of DNA that binds nuclear protein from human substantia nigrain vitroand functionally affects gene transcription. Furthermore, the −258 T/G polymorphism is genetically associated with idiopathic PD, as assessed in a large population-based series of cases and controls. Our results further implicate theparkingene in the development of Parkinson's disease.