Atsuta Naoki, Nakamura Ryoichi, Watanabe Hazuki, Watanabe Hirohisa, Ito Mizuki, Senda Jo, Tanaka Fumiaki, Sobue Gen
Department of Neurology, Nagoya University Graduate School of Medicine.
Rinsho Shinkeigaku. 2011 Nov;51(11):903-5. doi: 10.5692/clinicalneurol.51.903.
To investigate the longitudinal course of Japanese patients with Amyotrophic Lateral Sclerosis (ALS), we constructed a multicenter registration and follow-up system called Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS). Genomic DNA samples of ALS patients were stored and linked to the clinical information. We designed a telephone survey system using a clinical research coordinator (CRC) to check the score of the ALS Functional Rating Scale-R (ALSFRS-R) and the prognosis every 3 months. In January 2006, we began registering ALS patients, and, at present, 22 neurology facilities are participating in the JaCALS. Currently, 571 Japanese ALS patients are registered. From the longitudinal data of the 279 patients who were registered before September 2009, the older age at onset was a significant risk factor for not only earlier death or introduction of mechanical ventilation, but also earlier loss of speech, loss of swallowing function and loss of upper limb function. In collaboration with the RIKEN Center for Genomic Medicine, genome-wide association studies (GWAS) using 1,305 ALS samples from the JaCALS and BioBank Japan were conducted, which showed that ZNF512B gene was associated with susceptibility to ALS. The JaCALS has established an efficient registration and follow-up system with genomic DNA resources of ALS patients, and will contribute to identify ALS-associated genes and to promote clinical researches.
为了研究日本肌萎缩侧索硬化症（ALS）患者的疾病发展过程，我们构建了一个名为日本肌萎缩侧索硬化症研究联盟（JaCALS）的多中心登记和随访系统。ALS患者的基因组DNA样本被储存起来，并与临床信息相关联。我们设计了一个电话调查系统，由临床研究协调员（CRC）每3个月检查一次ALS功能评定量表修订版（ALSFRS-R）的评分和预后情况。2006年1月，我们开始登记ALS患者，目前有22个神经科机构参与了JaCALS。目前，已登记了571名日本ALS患者。从2009年9月之前登记的279名患者的纵向数据来看，发病时年龄较大不仅是过早死亡或开始使用机械通气的重要危险因素，也是过早丧失言语、吞咽功能和上肢功能的重要危险因素。我们与理化学研究所基因组医学中心合作，利用来自JaCALS和日本生物银行的1305份ALS样本进行了全基因组关联研究（GWAS），结果显示ZNF512B基因与ALS易感性相关。JaCALS利用ALS患者的基因组DNA资源建立了一个高效的登记和随访系统，将有助于识别与ALS相关的基因并推动临床研究。
