LEAD AND OTHER NEUROTOXINS AS RISK FACTORS FOR AMYOTROPHIC LATERAL SCLEROSIS

神经退行性疾病对公共卫生构成越来越大的挑战 随着人口老龄化。肌萎缩侧索硬化症(ALS)是一种神经病 运动系统的退行性疾病。其病因学本质上是 未知，但可能与环境神经毒素有关。病例对照 已经进行了ALS的研究，以调查累积的作用 终生接触铅；其他研究的神经毒素包括汞， 溶剂和杀虫剂。现场工作现已完成；110例肌萎缩侧索硬化症病例，30 诊所控制和270个人口控制已登记在册。铅 暴露的评估有三种方式：用x射线测量骨铅 荧光，一种创新的非侵入性技术；使用血铅 测量；并使用结构化的面对面访谈。初步 分析表明，血铅和骨铅有很强的相关性；两者 随着年龄的增长呈指数增长，但两者都与性别无关。 两者都与职业性铅暴露有关。调整后 就年龄和性别而言，血铅和骨铅水平在病例中都较高， 而且病例更有可能有职业性铅暴露。 将进行进一步的分析以证实这些发现并探索 其他神经毒素的影响。此外，饮食中的抗氧化剂 摄入量将被评估为一种保护因素和一种修饰 其他暴露与疾病的关系。相关基因的多态现象 异体代谢或与ALS相关的也将被研究， 使用PCR和RFLA，以便基因与环境的相互作用可以 已评估。阐明环境在ALS中的作用可能 促进采取措施预防这一毁灭性疾病，并可 此外，还为今后研究其他神经节细胞提供了一个范例。 生殖性疾病。

Neurodegenerative diseases pose an increasing challenge to public health as the population ages. Amyotrophic lateral sclerosis (ALS) is a neurod- egenerative disease of the motor system. Its etiology is essentially unknown, but environmental neurotoxins may be involved. A case-control study of ALS has been conducted to investigate the role of cumulative lifetime exposure to lead; other neurotoxins studied include mercury, solvents, and pesticides. Field work is now complete; 110 ALS cases, 30 clinic controls, and 270 population controls have been enrolled. Lead exposure was assessed in three ways: by measuring bone lead using x-ray fluorescence, an innovative noninvasive technique; with blood lead measurements; and using a structured in-person interview. 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 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 other 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 the environment in ALS may contribute to measures for prevention of this devastating disease and may in addition provide a paradigm for future studies of other neurode- generative diseases.