Kamel F, Umbach D M, Hu H, Munsat T L, Shefner J M, Taylor J A, Sandler D P
National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
Neurodegener Dis. 2005;2(3-4):195-201. doi: 10.1159/000089625.
The etiology of amyotrophic lateral sclerosis (ALS) likely involves an environmental component. We qualitatively assessed literature on ALS and lead exposure. Problems of study design make case reports and studies of lead in blood or tissues difficult to interpret. Most previous case-control studies found an association of ALS with self-reported occupational exposure to lead, with increased risks of 2- to >4-fold. However, these results may have been affected by recall bias.
To address inconsistencies among published reports, we used both lead biomarkers and interview data to assess lead exposure, and we evaluated the role of genetic susceptibility to lead.
We conducted a case-control study in New England in 1993-1996 with 109 ALS cases and 256 population-based controls. We measured blood and bone lead levels, the latter using X-ray fluorescence, and interviewed participants regarding sources of lead exposure.
In our study, ALS was associated with self-reported occupational lead exposure, with a dose response for cumulative days of exposure. ALS was also associated with blood and bone lead levels, with a 1.9-fold increase in risk for each mug/dl increment in blood lead and a 2.3- to 3.6-fold increase for each doubling of bone lead. A polymorphism in the delta-aminolevulinic acid dehydratase gene was associated with a 1.9-fold increase in ALS risk.
These results, together with previous studies, suggest that lead exposure plays a role in the etiology of ALS. An increase in mobilization of lead from bone into blood may play a role in the acute onset of disease.
肌萎缩侧索硬化症（ALS）的病因可能涉及环境因素。我们对有关ALS与铅暴露的文献进行了定性评估。研究设计问题使得病例报告以及血液或组织中铅含量的研究难以解读。此前大多数病例对照研究发现，ALS与自我报告的职业性铅暴露有关，风险增加2至4倍以上。然而，这些结果可能受到回忆偏倚的影响。
为解决已发表报告之间的不一致性，我们使用铅生物标志物和访谈数据来评估铅暴露情况，并评估铅的遗传易感性作用。
1993年至1996年，我们在新英格兰地区开展了一项病例对照研究，纳入109例ALS患者和256名基于人群的对照。我们测量了血液和骨骼中的铅含量，后者采用X射线荧光法，并就铅暴露源对参与者进行了访谈。
在我们的研究中，ALS与自我报告的职业性铅暴露有关，且与累积暴露天数存在剂量反应关系。ALS还与血液和骨骼中的铅含量有关，血铅每增加1微克/分升，风险增加1.9倍；骨铅含量每翻倍，风险增加2.3至3.6倍。δ-氨基乙酰丙酸脱水酶基因的多态性与ALS风险增加1.9倍有关。
这些结果与先前的研究共同表明，铅暴露在ALS的病因中起作用。骨骼中铅向血液中的动员增加可能在疾病的急性发作中起作用。
