LEAD AND OTHER NEUROTOXINS AS RISK FACTORS FOR AMYOTROPH

随着人口老龄化，神经退行性疾病对公共卫生构成越来越大的挑战。肌萎缩侧索硬化症（amyotrophic lateral sclerosis，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，但暴露于环境神经毒素可能发挥作用。我们进行了一项ALS的病例对照研究，以调查铅和其他神经毒素（包括汞、溶剂和农药）的累积终生暴露的影响。现场工作完成：110例ALS病例，31例临床对照和270例人群对照入组研究。我们通过三种方式评估铅暴露：我们使用X射线荧光（一种创新的非侵入性技术）测量骨铅;我们测量血铅;我们进行了一次结构化的面对面访谈，以收集有关潜在职业、住宅和生活方式暴露源的信息。ALS与血铅和骨铅水平的增加以及职业性铅暴露有关，但与居住或生活方式暴露无关。我们还发现ALS与吸烟有关，但与饮酒无关。ALS与抗氧化微量营养素或饮食中的其他成分关系不大。总的来说，这些结果扩展了以前的研究，表明铅暴露是ALS的一个危险因素。与血铅的关系是出乎意料的，并表明骨铅代谢可能是不同的ALS患者。进一步的分析将探讨ALS与其他神经毒性暴露的关系。此外，ALS与δ-氨基乙酰丙酸酯酶基因中常见多态性的关系将被研究，以进一步探索ALS与铅代谢之间的潜在关系。- 肌萎缩侧索硬化症、病例对照研究、铅、汞、溶剂、农药、吸烟、δ-氨基酮戊酸脱水酶-人类受试者和人类受试者：仅访谈、问卷调查或调查

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. ALS was associated with increased levels of both blood and bone lead and with occupational exposure to lead, but not with residential or lifestyle exposures. We also found that ALS was associated with cigarette smoking but not with alcohol use. There was little relationship of ALS with antioxidant micronutrients or other components of diet. Overall, these results extend previous studies to suggest that lead exposure is a risk factor for ALS. The relationship with blood lead was unexpected and suggests that metabolism of bone lead may be different in ALS patients. Further analyses will explore the relationship of ALS to other neurotoxic exposures. 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. - amyotrophic lateral sclerosis, case-control study, lead, mercury, solvents, pesticides, smoking, delta- aminolevulinic acid dehydratase - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only