Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease
Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease
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DOI：
10.1001/jama.286.18.2245
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发表时间：
2001-11-14
影响因子：
120.7
通讯作者：
Vance, JM
中科院分区：
文献类型：
--
作者：
Martin, ER;Scott, WK;Vance, JM
人类tau基因促进神经元微管的组装，与几种罕见的神经系统疾病有关，临床上包括帕金森病特征。我们最近观察到特发性帕金森病（PD）与染色体17 q21上含有tau基因的区域的联系。这些因素使tau蛋白成为研究特发性PD（最常见的疾病形式）易感基因的良好候选者。研究tau基因是否与特发性PD有关。设计、设置和参与者在来自235个家庭的1056个个体的样本中，所述家庭选自美国和澳大利亚的13个临床中心以及家庭确定核心中心，我们使用基于家族的关联性检验，检测了tau基因内的5个单核苷酸多态性（SNPs）与PD的关联性。纳入了受影响（n=426）和未受影响（n=579）的家庭成员; 51例患者的PD状态不明确。主要结果测量以家族为基础的关联性检验，使用渐近分布计算。结果SNP与PD之间的关联性分析为5个SNP中的3个提供了显著的关联性证据：SNP 3，P=.03; SNP 9 i，P=.04; SNP 11，P=.04。其他2个SNP没有显示出显著关联的证据（SNP 9 ii，P= 0.11和SNP 9 iii，P= 0.87）。单倍型分析发现了强有力的关联证据，与一种单倍型呈正相关（P=.009），与另一种单倍型呈负相关（P=.007）。连锁不平衡（P
Context The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease.Objective To: investigate whether the tau gene is involved in idiopathic PD.Design, Setting, and Participants Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n=426) and unaffected (n=579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene.Main Outcome Measure Family-based tests of association, calculated using asymptotic distributions.Results Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P=.03; SNP 9i, P=.04; and SNP 11, P=.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P=.11, and SNP 9iii, P=.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P=.009) and a negative association with another haplotype (P=.007). Substantial linkage disequilibrium (P