LEAD AND OTHER NEUROTOXINS AS RISK FACTORS FOR AMYOTROPH

工作摘要：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(ALS)是一种运动神经退行性疾病。其病因基本上尚不清楚，但暴露于环境神经毒素可能起到一定作用。我们对肌萎缩侧索硬化症进行了一项病例对照研究，以调查终生累积接触铅和其他神经毒素，包括汞、溶剂和杀虫剂的影响。现场工作已经完成：110例肌萎缩侧索硬化症患者、31名临床对照和270名人群对照纳入研究。我们通过三种方法评估铅暴露：我们使用x射线荧光测量骨铅，这是一种创新的非侵入性技术；我们测量血铅；我们进行结构化的面谈，以收集有关潜在的职业、居住和生活方式暴露来源的信息。肌萎缩侧索硬化症与血铅和骨铅水平的升高以及职业性铅暴露有关，但与住宅或生活方式的暴露无关。我们还发现肌萎缩侧索硬化症与吸烟有关，但与饮酒无关。ALS与抗氧化剂、微量营养素或其他饮食成分关系不大。总体而言，这些结果扩展了之前的研究，表明铅暴露是ALS的一个风险因素。这与血铅的关系是意想不到的，这表明ALS患者的骨铅代谢可能不同。进一步的分析将探索肌萎缩侧索硬化症与其他神经毒性暴露的关系。此外，还将研究ALS与β-氨基酮戊酸脱水酶基因的常见多态之间的关系，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，杀虫剂，吸烟，β-氨基乙酰丙酸脱水酶-人类受试者和人类受试者：访谈，问卷或调查

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