共济失调蛋白2三核苷酸重复长度与肌萎缩侧索硬化症风险相关。
ATXN2 trinucleotide repeat length correlates with risk of ALS.
作者信息
Sproviero William, Shatunov Aleksey, Stahl Daniel, Shoai Maryam, van Rheenen Wouter, Jones Ashley R, Al-Sarraj Safa, Andersen Peter M, Bonini Nancy M, Conforti Francesca L, Van Damme Philip, Daoud Hussein, Del Mar Amador Maria, Fogh Isabella, Forzan Monica, Gaastra Ben, Gellera Cinzia, Gitler Aaron D, Hardy John, Fratta Pietro, La Bella Vincenzo, Le Ber Isabelle, Van Langenhove Tim, Lattante Serena, Lee Yi-Chung, Malaspina Andrea, Meininger Vincent, Millecamps Stéphanie, Orrell Richard, Rademakers Rosa, Robberecht Wim, Rouleau Guy, Ross Owen A, Salachas Francois, Sidle Katie, Smith Bradley N, Soong Bing-Wen, Sorarù Gianni, Stevanin Giovanni, Kabashi Edor, Troakes Claire, van Broeckhoven Christine, Veldink Jan H, van den Berg Leonard H, Shaw Christopher E, Powell John F, Al-Chalabi Ammar
机构信息
Department of Basic and Clinical Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.
Department of Biostatistics, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
出版信息
Neurobiol Aging. 2017 Mar;51:178.e1-178.e9. doi: 10.1016/j.neurobiolaging.2016.11.010. Epub 2016 Nov 24.
We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.
我们对肌萎缩侧索硬化症（ALS）患者的ATXN2基因中的CAG三核苷酸重复序列扩增进行了研究。分析了两项新的病例对照研究，一个是包含1474例ALS病例和567名对照的英国数据集，另一个是包含1328例ALS病例和691名对照的荷兰数据集。此外，为了增强检验效能，我们系统检索了PubMed中2010年8月1日之后发表的研究ATXN2中间重复序列与ALS之间关联的病例对照研究。我们对新的和现有的研究进行了荟萃分析，以探讨携带24至34个CAG三核苷酸重复序列的ATXN2中间重复等位基因与ALS的相对风险。携带中等大小三核苷酸重复等位基因的个体患ALS的总体风险增加（优势比3.06 [95%置信区间2.37 - 3.94]；p = 6 × 10），对于29 - 32个重复序列的等位基因，重复长度与ALS风险之间存在指数关系（R = 0.91，p = 0.0002）。未发现重复长度与发病年龄或生存率之间存在关联。与三核苷酸重复疾病不同，ALS中ATXN2中间三核苷酸重复序列扩增不能预测发病年龄，但可预测疾病风险。
Zotero 插件