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

基于人群的俄亥俄州 ALS 数据库和 ALS 危险因素的病例对照研究

• 批准号: 9047656
• 负责人: Angeline Sanderson Andrew
• 金额: $ 40万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9047656
• 关键词: Population; Based; Ohio; ALS; Repository

 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.

 描述（由申请方提供）：导致致死性神经退行性疾病肌萎缩侧索硬化症（ALS）的散发（非家族性）形式的主要病因仍不清楚。国家ALS登记处收集通过在线门户网站登记的患者的环境风险因素信息。然而，目前尚不清楚国家ALS登记处的风险因素数据与整个ALS患者人群相比具有多大的代表性。我们将制定一项监测计划，以完全确定北方/中部俄亥俄州的ALS病例（具体目标1）。我们将根据从俄亥俄州监测项目中收集的患者和从同一地区随机选择的人群对照受试者（特定目标2）中使用专门设计的环境问卷收集的数据，对ALS的风险因素进行人群病例对照研究。我们将比较ALS患者与随机对照组暴露于蓝藻神经毒素β-N-甲氨基-L-丙氨酸（BMAA）和其他环境毒物（包括铅、汞和农药）的水平，这些毒物是散发性ALS的潜在危险因素。中心假设是，在易感个体中，发生ALS的风险随着暴露于这些风险因素的剂量和持续时间而增加。将通过以下方式确定接触情况：（一）使用问卷调查数据，接触蓝细菌的历史和从事高风险职业的历史;（二）使用鱼类消费问卷数据和鱼类甲基汞数据库，从饮食中摄入汞;以及（三）居民接触环境毒素/毒物的地理空间分布。风险暴露绘图将包括：（一）终生居住史;（二）潜在环境毒物来源（布朗菲尔德和超级基金场地、危险废物场地、农药）和水体中的蓝细菌（具体目标3）。该地理绘图项目将是一项对俄亥俄州ALS监测项目患者和普通人群随机对照暴露的病例对照研究。整个北方/中部俄亥俄州的水体中的蓝藻含量将使用直接采样和气溶胶收集水体，校准卫星遥感相结合的方式来确定。我们的方法是创新的;这是俄亥俄州第一个全面的ALS监测计划，该州有许多危险废物，也与伊利湖接壤，伊利湖有大量的蓝藻水华;这是第一次深入分析暴露于蓝藻作为俄亥俄州ALS的风险因素;这是第一次使用地理空间测绘对ALS的全部范围的牵连环境风险因素的相对风险进行全面分析。确定增加ALS风险的特定环境毒素/毒物将使减少暴露措施能够预防这种使人衰弱和致命的疾病。