ATXN2 PolyQ中间重复修改ALS表型和生存(P2.005)

文摘

目标。分析的频率和临床特点ALS患者中间长度(CAG)扩张(编码即谷氨酰胺,polyQ)在以人群为基础的队列的意大利ATXN2基因病人(发现队列特区),和连续复制一个独立队列的结果从一个ALS患者三级中心(验证队列,VC)。背景。ATXN2 polyQ中间重复已报告代表ALS的危险因素。没有执行研究它们对表型的影响。设计/方法。直流包含在2007 - 2012年672例事件在皮埃蒙特和瓦莱达奥斯塔地区,意大利;509年控制神经健康主题,研究地区的居民,年龄——准确性情况。VC中包括661名ALS患者连续见过2001年和2013年之间在ALS诊所的中心在罗马天主教大学,意大利。结果。 In the DC the frequency of 蠅31 polyQ ATNX2 repeats was significantly more common in ALS cases (19 patients vs. 1 control, p=0.0001; odds ratio 14.8, 95[percnt] c.i., 1.9-110.8). Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (median survival 1.8 years, interquartile range [IQR] 1.3-2.2 vs. 2.7 years, IQR 1.6-5.1) (p=0.001), and an increase frequency of spinal onset. 蠅31 polyQ ATNX2 repeats remained independently significant in multivariable analysis. In the VC, patients with 蠅31polyQ repeats have a shorter survival than those with <31 repeats (median survival, polyQ 蠅31, 2.0 years, IQR 1.5-3.4; polyQ <31, 3.2 years, IQR 2.0-6.4; p=0.007). Conclusions. ATXN2 polyQ intermediate repeat is a modifier of ALS survival and phenotype. Disease-modifying therapies targeted to ATXN2 represent a promising therapeutic approach for ALS. Study supported by Ministero della Salute (grant RF-2010-2309849), European Community’s Health Seventh Framework Programme (grant agreement 259867), ARISLA (RepeatALS project).

披露:没有卡尔沃博士没有披露。Moglia博士没有披露。Canosa博士没有披露。Restagno博士没有披露。Brunetti博士没有披露。barberi博士没有披露。孔蒂博士没有披露。博士Marangi称没有披露。Lattante博士没有披露。Zollino博士没有披露。 Dr. Sabatelli has nothing to disclose. Dr. Corrado has nothing to disclose. Dr. Mora has nothing to disclose. Dr. Mazzini has nothing to disclose. Dr. D'Alfonso has nothing to disclose.