LEAD AND OTHER NEUROTOXINS AS RISK FACTORS FOR AMYOTROPH

工作总结：神经退行性疾病构成越来越大的挑战 对公共卫生的影响 肌萎缩侧索硬化 (ALS)是一种运动系统的神经退行性疾病 其病因 基本上是未知的，但环境神经毒素可能参与其中。 我们对ALS进行了一项病例对照研究，以探讨以下因素的作用 终生累积接触铅和其他神经毒素，包括 汞、溶剂和杀虫剂。 现场工作完成; 110名ALS 31例临床对照和270例人群对照被纳入研究。 书房 我们通过三种方式评估铅暴露： 使用X射线荧光，一种创新的非侵入性技术，我们 测量血铅;我们进行了一次结构化的面对面访谈， 收集有关潜在职业、住宅和 暴露的生活方式来源。 初步分析显示， 和骨铅密切相关;两者均呈指数增长， 年龄，但两者都与性别无关。 两者都与 职业接触铅。 在调整年龄和性别后， ALS患者血铅和骨铅水平较高， 可能有职业性铅暴露。 进一步的分析将在 为了证实这些发现，并探索其他因素的影响， 神经毒素 此外，还将评估膳食抗氧化剂摄入量 作为一种保护因素和作为一种疾病的修饰剂， 关系。外源性物质代谢相关基因的多态性 或与ALS相关的研究，使用PCR和RFLA， 基因与环境的相互作用是可以评估的。 阐明作用 ALS中的环境神经毒素可能有助于测量 预防这种毁灭性的疾病，并可能提供一个 为今后研究其他神经退行性疾病提供范例。

Summary of Work: Neurodegenerative diseases pose an increasing challenge to public health as the population ages. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system. Its etiology is essentially unknown, but environmental neurotoxins may be involved. We have conducted a case-control study of ALS to investigate the role of cumulative lifetime exposure to lead and other neurotoxins, including mercury, solvents, and pesticides. Field work is complete; 110 ALS cases, 31 clinic controls, and 270 population controls were enrolled in the study. We assessed lead exposure in three ways: we measured bone lead using x-ray fluorescence, an innovative noninvasive technique; we measured blood lead; and we administered a structured in-person interview to gather information on potential occupational, residential, and lifestyle sources of exposure. Preliminary analyses showed that blood and bone lead were strongly correlated; both increased exponentially with age, but neither was associated with gender. Both were associated with occupational exposure to lead. After adjusting for age and gender, both blood and bone lead levels were higher in ALS cases, and cases were more likely to have occupational exposure to lead. Further analyses will be conducted to confirm these findings and explore the effects of other neurotoxins. In addition, dietary antioxidant intake will be evaluated as a protective factor and as a modifier of exposure-disease relationships. Polymorphisms in genes involved in xenobiotic metabolism or associated with ALS will also be studied, using PCR and RFLA, so that gene-environment interactions can be evaluated. Elucidation of the role of environmental neurotoxins in ALS may contribute to measures for prevention of this devastating disease and may in addition provide a paradigm for future studies of other neurodegenerative diseases.