LEAD AND OTHER NEUROTOXINS AS RISK FACTORS FOR AMYOTROPH

工作总结：神经退行性疾病 随着人口老龄化，对公共卫生构成越来越大的挑战。 肌萎缩侧索硬化症（ALS）是一种神经退行性疾病 的运动系统。其病因基本上是未知的，但 暴露于环境神经毒素可能起作用。我们 进行了一项ALS病例对照研究，以调查 终生累积接触铅和其他神经毒素， 包括汞、溶剂和杀虫剂。实地工作完成; 110例ALS病例、31例临床对照和270例人群对照 参加了这项研究。我们评估了三个国家的铅暴露情况， 方法：采用X射线荧光法测定骨铅含量， 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， 潜在的职业，住宅和生活方式来源， exposure.迄今为止的结果表明，ALS与以下因素密切相关： 血铅和骨铅含量都很高与血铅的关系 这是出乎意料的，并表明骨铅的代谢可能是 与ALS患者不同。ALS也与 职业接触铅，但不与住宅或 娱乐性暴露。总的来说，这些结果扩展了以前的结果。 研究表明，铅暴露是ALS的一个危险因素。我们 还发现ALS与吸烟有关。进一步 分析将探讨ALS与其他神经毒性的关系， 暴露和饮食抗氧化剂。此外，关系 ALS的一个常见的多态性基因， 将对δ-氨基乙酰丙酸脱氢酶进行研究， 进一步研究ALS和铅之间的潜在关系 新陈代谢.

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 exposure to environmental neurotoxins may play a role. We conducted a case-control study of ALS to investigate the effects 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. Results to date show that ALS is strongly associated with both blood and bone lead levels. The relationship with blood lead was unexpected and suggests that metabolism of bone lead may be different in ALS patients. ALS was also associated with occupational exposure to lead, but not with residential or recreational exposures. Overall, these results extend previous studies to suggest that lead exposure is a risk factor for ALS. We also found that ALS was associated with cigarette smoking. Further analyses will explore the relationship of ALS to other neurotoxic exposures and to dietary antioxidants. In addition, the relationship of ALS to a common polymorphism in the gene for delta-aminolevulinic acid dehydratase will be studied to explore further the potential relationship between ALS and lead metabolism.