Association of MAPT haplotype-tagging SNPs with sporadic Parkinson's disease
Association of MAPT haplotype-tagging SNPs with sporadic Parkinson's disease
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DOI：
10.1016/j.neurobiolaging.2007.11.019
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发表时间：
2009-09-01
影响因子：
4.2
通讯作者：
de Silva, Rohan
中科院分区：
文献类型：
--
作者：
Vandrovcova, Jana;Pittman, Alan M.;de Silva, Rohan
tau基因（MAPT）突变已在与17号染色体相关的额颞叶痴呆伴帕金森综合征家族中发现。此外，MAPT H1-进化枝特异性亚单倍型H1 c与tau蛋白病、进行性核上性麻痹（PSP）和皮质基底节变性（CBD）密切相关，并且在较小程度上与阿尔茨海默病（AD）密切相关。在帕金森病（PD）中，有几份报告与MAPT H1进化枝相关。虽然弱到不确定，但这种关联得到了各种研究荟萃分析的支持。为了进一步研究MAPT在PD中的这种令人困惑的作用，对一大群散发性PD病例中的六个单倍型标记SNP进行了基因分型; 324例病理确诊，248例临床诊断，以及660例对照。在单位点关联分析中，H1进化枝与PD风险增加相关（p = 0.032）。在单倍型分析中，与对照相比，唯一的H2衍生的单倍型在所有PD病例中代表性不足（p = 0.03）。来自H1进化枝背景的任何常见单倍型的分布没有显着差异。我们的研究支持了MAPT基因的遗传变异性赋予PD易感性的假设。然而，这种影响并不强烈，并且不涉及H1 c单倍型，这表明一种机制与相关tau蛋白病中所涉及的机制不同，并且可以通过H1/H2倒置来解释。(C)2007年爱思唯尔公司All rights reserved.
Mutations in the tau gene (MAPT) have been found in families with frontotemporal dementia with parkinsonism linked to chromosome 17. In addition, the MAPT H1-clade specific sub-haplotype, H1c, has been strongly associated with the tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and, to a lesser extent, with Alzheimer's disease (AD). In Parkinson's disease (PD), there have been several reports of association with the MAPT H1-clade. Although weak to inconclusive, this association is supported by metaanalyses of the various studies. To further investigate this baffling role of MAPT in PD, six haplotype-tagging SNPs were genotyped in a large cohort of sporadic PD cases; 324 pathologically confirmed and 248 clinically diagnosed, and 660 controls. In the single-locus association analysis, the H1-clade was associated with an increased risk of PD (p = 0.032). In the haplotype-analysis, the sole H2-derived haplotype was under-represented in all of the PD cases compared to controls (p = 0.03). There was no significant difference in the distribution of any of the common haplotypes derived from the H1-clade background. Our study supports the hypothesis that genetic variability in the MAPT gene confers susceptibility to PD. However, the effect is not strong, and the H1c haplotype is not involved, suggesting a mechanism that is distinct to that involved in the associated tauopathies and may be explained by the H1/H2 inversion. (C) 2007 Elsevier Inc. All rights reserved.