ATXN1 intermediate-length polyglutamine expansions are associated with amyotrophic lateral sclerosis
ATXN1 intermediate-length polyglutamine expansions are associated with amyotrophic lateral sclerosis
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DOI：
10.1016/j.neurobiolaging.2017.11.011
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发表时间：
2018-04-01
影响因子：
4.2
通讯作者：
Sabatelli, Mario
中科院分区：
文献类型：
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作者：
Lattante, Serena;Pomponi, Maria Grazia;Sabatelli, Mario
为了阐明中间ATXN 1等位基因作为肌萎缩侧索硬化症（ALS）危险因素的可能参与，我们在1146名意大利ALS患者队列中测试了ATXN 1，先前筛选了其他ALS基因的变体，并在529名对照中进行了测试。我们在1146例患者中的105例（9.16%）和529例对照中的29例（5.48%）中检测到ATXN 1等位基因≥ 33个多聚谷氨酰胺重复（p = 0.003）。在携带C9 orf 72扩增的ALS患者组中，具有>= 33个多聚谷氨酰胺重复的ATXN 1等位基因的频率特别高（12/59，20.3%）。我们在C9 orf 72意大利患者的独立队列中证实了这一结果（10/80例，12.5%），因此发现C9 orf 72携带者中ATXN 1扩增的累积频率为15.82%（p = 2.40E-05）。我们的研究结果强烈支持这一假设，ATXN 1可以作为一个疾病的风险基因在ALS，主要是在C9 orf 72扩展运营商。需要进一步的研究来证实我们的结果，并确定ATXN 1可能有助于导致ALS的神经元变性的机制。(C)2017爱思唯尔公司All rights reserved.
To clarify the possible involvement of intermediate ATXN1 alleles as risk factors for amyotrophic lateral sclerosis (ALS), we tested ATXN1 in a cohort of 1146 Italian ALS patients, previously screened for variants in other ALS genes, and in 529 controls. We detected ATXN1 alleles with >= 33 polyglutamine repeats in 105 of 1146 patients (9.16%) and 29 of 529 controls (5.48%) (p = 0.003). The frequency of ATXN1 alleles with >= 33 polyglutamine repeats was particularly high in the group of ALS patients carrying the C9orf72 expansion (12/59, 20.3%). We confirmed this result in an independent cohort of C9orf72 Italian patients (10/80 cases, 12.5%), thus finding a cumulative frequency of ATXN1 expansion of 15.82% in C9orf72 carriers (p = 2.40E-05). Our results strongly support the hypothesis that ATXN1 could act as a disease risk gene in ALS, mostly in C9orf72 expansion carriers. Further studies are needed to confirm our results and to define the mechanism by which ATXN1 might contribute to neuronal degeneration leading to ALS. (C) 2017 Elsevier Inc. All rights reserved.