Role of the Tau Gene Region Chromosome Inversion in Progressive Supranuclear Palsy, Corticobasal Degeneration, and Related Disorders
Role of the Tau Gene Region Chromosome Inversion in Progressive Supranuclear Palsy, Corticobasal Degeneration, and Related Disorders
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DOI：
10.1001/archneur.65.11.1473
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发表时间：
2008-11-01
影响因子：
--
通讯作者：
Wilhelmsen, Kirk C.
中科院分区：
文献类型：
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作者：
Webb, Amy;Miller, Bruce;Wilhelmsen, Kirk C.
背景：17号染色体上的一个倒位区域先前已与许多Pick复合体疾病相关。由于倒位，很难确定确切的致病基因座，但微管相关蛋白tau基因是一个可能的候选基因，它参与了这些疾病与tau inclusion。目的：寻找变异，赋予易感性4 tau蛋白病和临床相关疾病。设计：全基因组关联研究。设置：大学研究实验室。参与者：对来自一个不相关的白色人群的进行性核上性麻痹（PSP）、皮质基底节变性（CBD）、额颞叶痴呆和额颞叶痴呆伴肌萎缩的患者共231个样本进行基因分型。来自同一人群的未受影响的个体被用作controls.Main结果测量：从17号染色体的一个倒位区域，包含MAPT基因的结果。病例组和对照组的基因型采用Fisher精确检验进行比较。单倍型通过目视检查genotype.Results确定：比较任何特定的疾病和对照，协会是恒定的整个倒置染色体片段。PSP和PSP与CBD的结合具有显著的相关性。在该地区看到的2个单倍型，H1是过度的PSP和CBD的情况下，与controls.Conclusions相比：正如预期的那样，标记高度相关，并在整个地区的关联，这使得它很难缩小致病变异，甚至可能的候选基因。然而，考虑到这些疾病的病理异常和家族性形式中所见的tau突变的参与，MAPT基因代表了驱动该关联的最可能原因。
Background: An inverted region on chromosome 17 has been previously linked to many Pick complex diseases. Due to the inversion, an exact causal locus has been difficult to identify, but the microtubule-associated protein tau gene is a likely candidate gene for its involvement in these diseases with tau inclusion.Objective: To search for variants that confer susceptibility to 4 tauopathies and clinically related disorders.Design: Genomewide association study.Setting: University research laboratory.Participants: A total of 231 samples were genotyped from an unrelated white population of patients with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia, and frontotemporal dementia with amyotrophy. Unaffected individuals from the same population were used as controls.Main Outcome Measures: The results from an inverted region of chromosome 17 that contains the MAPT gene. Genotypes of cases and controls were compared using a Fisher exact test on a marker-by-marker basis. Haplotypes were determined by visually inspecting genotypes.Results: Comparing any particular disease and controls, the association was constant across the inverted chromosome segment. Significant associations were seen for PSP and PSP combined with CBD. Of the 2 haplotypes seen in the region, H1 was overrepresented in PSP and CBD cases compared with controls.Conclusions: As expected, the markers are highly correlated and the association is seen across the entire region, which makes it difficult to narrow down a disease-causing variant or even a possible candidate gene. However, considering the pathologic abnormalities of these diseases and the involvement of tau mutations seen in familial forms, the MAPT gene represents the most likely cause driving the association.