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。脊髓运动神经元的退化会导致肌肉萎缩和虚弱，而大脑皮层运动神经元的退化会导致反射亢进。肌萎缩侧索硬化症进展迅速；患者通常在发病后两到五年内死亡。肌萎缩侧索硬化症的年发病率是每10万人中就有一到两人。这一比率随着年龄的增长而增加，男性的比例高于女性。大约5%到10%的ALS病例有ALS家族史。一般说来，ALS的病因尚不清楚，尽管遗传因素与家族性形式有关。环境暴露也被认为是ALS的潜在原因。现有证据最清楚地表明了接触重金属，特别是铅的作用，尽管电磁场和包括杀虫剂和溶剂在内的化学暴露也有牵连。 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。研究的主要目的是评估铅暴露与肌萎缩侧索硬化症的关系。我们通过结构化访谈收集了有关铅的职业、居住和娱乐暴露的信息。此外，我们还测量了血铅和骨铅水平，后者通过体内K-X-射线荧光(K-XRF)进行测量。据我们所知，以前没有研究报告用这种技术测量ALS病例的骨铅水平。 在一项病例对照研究中，我们通过生物测量和访谈评估了铅暴露与肌萎缩侧索硬化症的关系。病例(N=109)在马萨诸塞州波士顿的两家医院招募。通过随机数字拨号确定的人群对照(N=256)与新英格兰地区内的年龄、性别和居住地区的病例进行频率匹配。 肌萎缩侧索硬化症的风险与自我报告的职业性铅暴露增加两倍相关，并具有终生铅暴露天数的剂量反应。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道一致，表明铅暴露在肌萎缩侧索硬化症的病因中具有潜在的作用。 我们还评估了ALS与铅遗传易感性的关系。ALAD2等位基因与膝盖骨和胫骨的铅水平降低有关，但与血铅水平无关，并与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肌萎缩侧索硬化症无关。

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.