A Population-Based Ohio ALS Repository and a Case-Control Study of ALS Risk Factors

 描述(由申请人提供)：导致致死性神经退行性疾病肌萎缩侧索硬化症(ALS)的散发性(非家族性)形式的主要病因尚不清楚。国家肌萎缩侧索硬化症注册中心从通过在线门户注册的患者那里收集有关环境风险因素的信息。然而，目前尚不清楚全国肌萎缩侧索硬化症登记处的风险因素数据与整个肌萎缩侧索硬化症患者群体相比有多大的代表性。我们将制定一项监测计划，以实现对俄亥俄州北部/中部ALS病例的完全查明(具体目标1)。我们将根据俄亥俄州监测项目中收集的患者的特殊设计的环境问卷收集的数据，以及从同一地区随机选择的人口控制对象(特定目标2)，对ALS的危险因素进行人口病例对照研究。我们将比较肌萎缩侧索硬化症患者和随机对照组在暴露于蓝藻神经毒素、β-N-甲氨基-L-丙氨酸(BMAA)以及其他环境毒物(包括铅、汞和杀虫剂)作为散发性肌萎缩侧索硬化症潜在危险因素的水平。中心假设是，在易感个体中，发生肌萎缩侧索硬化症的风险随着暴露于这些危险因素的剂量和时间而增加。暴露量将由以下因素确定：(1)接触蓝藻和从事危险职业的历史，使用问卷数据；(2)汞的膳食摄入量，使用关于鱼类消费的问卷数据和鱼类中甲基汞的数据库；(3)居民暴露于环境毒素/毒物的地理空间分布。风险暴露测绘将包括：(1)终身居住史；(2)潜在环境毒物(棕地和超级基金场地、危险废物场地、农业杀虫剂)和水体中蓝藻的来源(具体目标3)。地理测绘计划将是对俄亥俄州ALS监测计划患者的暴露和普通人群的随机对照的病例对照研究。整个北/中俄亥俄州水体中蓝藻的含量将使用直接采样和从水体中收集气溶胶以及校准卫星遥感相结合的方法来确定。我们的方法是创新的；这是俄亥俄州的第一个全面的肌萎缩侧索硬化症监测项目，该州拥有许多危险废物场地，也毗邻拥有大规模蓝藻水华的伊利湖；这是第一次深入分析暴露于蓝藻作为俄亥俄州肌萎缩侧索硬化症的风险因素；这是第一次使用地球空间地图对肌萎缩侧索硬化症的各种被牵连的环境风险因素的相对风险进行全面分析。确定增加肌萎缩侧索硬化症风险的特定环境毒素/毒物将有助于减少接触，以预防这种虚弱和致命的疾病。

 DESCRIPTION (provided by applicant): The primary etiologic factors leading to the sporadic (non-familial) form of the lethal neurodegenerative disease amyotrophic lateral sclerosis (ALS) remain unknown. The National ALS Registry collects information on environmental risk factors from patients who register through the on-line portal. However, it is not known how representative the risk factor data in the National ALS Registry are in comparison with the population of ALS patients as a whole. We will develop a surveillance program that will achieve complete ascertainment of ALS cases in Northern / Central Ohio (Specific Aim 1). We will conduct a population case control study of risk factors for ALS based on data collected with a specially designed environmental questionnaire from the patients collected in the Ohio surveillance program and randomly selected population control subjects from the same region (Specific Aim 2). We will compare ALS patients to random controls with regard to levels of exposure to the cyanobacterial neurotoxin, β-N-methylamino-L-alanine (BMAA), and other environmental toxicants, including lead, mercury and pesticides, as potential risk factors for sporadic ALS. The central hypothesis is that the risk of developing ALS increases with dose and duration of exposure to these risk factors in susceptible individuals. Exposures will be determined by: (i) history of exposure to cyanobacteria and involvement in at-risk occupations, using questionnaire data; (ii) dietary intake of mercury, using questionnaire data on fish consumption and databases of methylmercury in fish; and (iii) the geospatial distribution of residential exposure to environmental toxins/toxicants. Mapping of at-risk exposures will include: (i) lifetime residential histories; (ii) sources of potential environmental toxicants (Brownfield ad Superfund sites, hazardous waste sites, agricultural pesticides) and cyanobacteria in waterbodies (Specific Aim 3). The geographical mapping program will be a case control study of exposures in Ohio ALS surveillance program patients and random controls from the general population. The content of cyanobacteria in waterbodies throughout Northern / Central Ohio will be determined using a combination of direct sampling and aerosol collections from waterbodies, and calibrated satellite remote sensing. Our approach is innovative; it is the first comprehensive ALS surveillance program in Ohio, a state with many hazardous waste sites that also borders Lake Erie, which has massive cyanobacterial blooms; it is the first in-depth analysis of exposure to cyanobacteria as a risk factor for ALS in Ohio; and it is the first comprehensive analysis of th relative risks of the full range of incriminated environmental risk factors for ALS using geospatia mapping. Identifying the specific environmental toxins/toxicants that increase risk of ALS will enable exposure reduction initiatives to prevent this debilitating and lethal disease.