ATXN2 polyQ intermediate repeats are a modifier of ALS survival
ATXN2 polyQ intermediate repeats are a modifier of ALS survival
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DOI：
10.1212/wnl.0000000000001159
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发表时间：
2015-01-20
期刊：
影响因子：
9.9
通讯作者：
Bottacchi, Edo
中科院分区：
文献类型：
--
作者：
Chio, Adriano;Calvo, Andrea;Bottacchi, Edo
目的：分析意大利肌萎缩侧索硬化症(ALS)患者中ATXN2基因中长(CAG，编码27-33个谷氨酸，PolyQ)扩增(编码27-33个谷氨酸，PolyQ)的频率和临床特征，并在ALS三级中心(验证队列)的独立队列中重复研究结果。方法：对2007-2012年意大利Piemonte和Valle d‘Aosta地区发生的672例ALS患者(发现队列)进行多聚Q重复序列评估；对照组为509名神经学健康、年龄和性别匹配的研究地区居民。验证队列包括2001年至2013年在意大利罗马天主教大学肌萎缩侧索硬化症临床中心连续就诊的661例肌萎缩侧索硬化症患者。结果：在发现的队列中，肌萎缩侧索硬化症患者中>；=31个PolyQ ATNX2重复频率明显更常见(19例患者与1例对照，p=0.0001；优势比14.8，95%可信区间1.9-110.8)。多Q重复数增加的患者比=31，1.8年，四分位数范围[IQR]1.3-2.2；多Q=31，2.0年，IQR 1.5-3.4的患者生存期短
Objective: To analyze the frequency and clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) with intermediate-length (CAG) expansion (encoding 27-33 glutamines, polyQ) in the ATXN2 gene, in a population-based cohort of Italian patients with ALS (discovery cohort), and to replicate the findings in an independent cohort of consecutive patients from an ALS tertiary center (validation cohort).Methods: PolyQ repeats were assessed in 672 patients with incident ALS in Piemonte and Valle d'Aosta regions, Italy, in the 2007-2012 period (discovery cohort); controls were 509 neurologically healthy age-and sex-matched subjects resident in the study area. The validation cohort included 661 patients with ALS consecutively seen between 2001 and 2013 in the ALS Clinic Center of the Catholic University in Rome, Italy.Results: In the discovery cohort, the frequency of >= 31 polyQ ATNX2 repeats was significantly more common in ALS cases (19 patients vs 1 control, p = 0.0001; odds ratio 14.8, 95% confidence interval 1.9-110.8). Patients with an increased number of polyQ repeats had a shorter survival than those with = 31, 1.8 years, interquartile range [IQR] 1.3-2.2; polyQ = 31 polyQ repeats had a shorter survival than those with = 31, 2.0 years, IQR 1.5-3.4; polyQ