Lead And Other Neurotoxins As Risk Factors For Amyotroph

肌萎缩侧索硬化症（ALS）是一种影响脊髓和大脑运动神经元的神经退行性疾病。脊髓运动神经元的变性导致肌肉萎缩和虚弱，而大脑皮层中运动神经元的变性导致反射亢进。ALS进展迅速;患者通常在发病后两到五年内死亡。ALS的年发病率为十万分之一到二。这一比率随着年龄的增长而增加，男性高于女性。大约5%至10%的ALS病例有ALS家族史。一般来说，ALS的病因仍然不清楚，尽管遗传因素参与了家族形式。环境暴露也被认为是ALS的潜在原因。现有的证据最清楚地表明，接触重金属，特别是铅的作用，虽然电磁场和化学品接触，包括农药和溶剂也有牵连。 我们从1993年到1996年在新英格兰进行了一项ALS的病例对照研究。这项研究的主要目的是评估铅暴露与ALS的关系。我们收集的信息，职业，住宅和娱乐接触铅使用结构化访谈。此外，我们还测量了血液和骨铅水平，后者通过体内K X射线荧光（K-XRF）。据我们所知，没有以前的研究报告骨铅水平的ALS病例测量这种技术。 我们评估了铅暴露与ALS的关系，采用生物学措施和访谈，在病例对照研究。在马萨诸塞州波士顿的两家医院招募病例（N=109）。通过随机数字拨号确定的人群对照（N=256）与新英格兰内年龄、性别和居住地区的病例频率匹配。 ALS的风险与自我报告的职业铅暴露的两倍增加有关，并与铅暴露的剂量反应有关。ALS的风险也与血铅和骨铅水平的升高有关。这些结果与以前的报告是一致的，并建议在ALS的病因铅暴露的潜在作用。 我们还评估了ALS与铅遗传易感性的关系。ALAD 2等位基因与髌骨和胫骨的铅水平降低相关，但与血铅水平无关，并且与ALS风险增加两倍相关。相反，维生素D受体B等位基因与铅水平或ALS无关。

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor neurons of the spinal cord and brain. Degeneration of spinal motor neurons leads to muscular atrophy and weakness, while degeneration of motor neurons in the cerebral cortex leads to hyperreflexia. ALS is rapidly progressive; patients generally die within two to five years of onset. The annual incidence rate of ALS is one to two per 100,000. This rate increases with age and is greater in men than in women. Approximately 5 to 10% of ALS cases have a family history of ALS. In general, the etiology of ALS remains unclear, although genetic factors are involved in the familial form. Environmental exposures have also been considered as potential causes of ALS. Existing evidence has most clearly suggested a role for exposure to heavy metals, particularly lead, although electromagnetic fields and chemical exposures including pesticides and solvents have also been implicated. We conducted a case-control study of ALS in New England from 1993 to 1996. The primary purpose of the study was to evaluate the relationship of lead exposure to ALS. We collected information on occupational, residential, and recreational exposure to lead using a structured interview. In addition, we measured blood and bone lead levels, the latter via in vivo K x-ray fluorescence (K-XRF). To our knowledge, no previous studies have reported bone lead levels in ALS cases measured with this technique. We evaluated the relation of lead exposure to ALS, using both biological measures and interviews, in a case-control study. Cases (N=109) were recruited at two hospitals in Boston, MA. Population controls (N=256) identified by random digit dialing were frequency-matched to cases by age, sex, and region of residence within New England. Risk of ALS was associated with a two-fold increase in self-reported occupational exposure to lead, with a dose-response for lifetime days of lead exposure. Risk of ALS was also associated with elevations in both blood and bone lead levels. These results are consistent with previous reports and suggest a potential role for lead exposure in the etiology of ALS. We also evaluated the relationship of ALS to genetic susceptibility to lead. The ALAD2 allele was associated with decreased lead levels in both patella and tibia, although not with blood lead levels, and with a two-fold increased risk of ALS. In contrast, the vitamin D receptor B allele was not associated with lead levels or ALS.