Ji John S, Power Melinda C, Sparrow David, Spiro Avron, Hu Howard, Louis Elan D, Weisskopf Marc G
Department of Environmental Health, and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Environ Health Perspect. 2015 May;123(5):445-50. doi: 10.1289/ehp.1408535. Epub 2015 Jan 23.
Tremor is one of the most common neurological signs, yet its etiology is poorly understood. Case-control studies suggest an association between blood lead and essential tremor, and that this association is modified by polymorphisms in the δ-aminolevulinic acid dehydrogenase (ALAD) gene.
We aimed to examine the relationship between lead and tremor, including modification by ALAD, in a prospective cohort study, using both blood lead and bone lead-a biomarker of cumulative lead exposure.
We measured tibia (n = 670) and patella (n = 672) bone lead and blood lead (n = 807) among older men (age range, 50-98 years) in the VA Normative Aging Study cohort. A tremor score was created based on an approach using hand-drawing samples. ALAD genotype was dichotomized as ALAD-2 carriers or not. We used linear regression adjusted for age, education, smoking, and alcohol intake to estimate the associations between lead biomarkers and tremor score.
In unadjusted analyses, there was a marginal association between quintiles of all lead biomarkers and tremor scores (p-values < 0.13), which did not persist in adjusted models. Age was the strongest predictor of tremor. Among those younger than the median age (68.9 years), tremor increased significantly with blood lead (p = 0.03), but this pattern was not apparent for bone lead. We did not see modification by ALAD or an association between bone lead and change in tremor score over time.
Our results do not strongly support an association between lead exposure and tremor, and suggest no association with cumulative lead biomarkers, although there is some suggestion that blood lead may be associated with tremor among the younger men in our cohort.
震颤是最常见的神经学体征之一，但其病因仍知之甚少。病例对照研究表明血铅与特发性震颤之间存在关联，且这种关联会因δ-氨基乙酰丙酸脱氢酶（ALAD）基因的多态性而改变。
在一项前瞻性队列研究中，我们旨在使用血铅和骨铅（一种累积铅暴露的生物标志物）来研究铅与震颤之间的关系，包括ALAD基因的影响。
在退伍军人事务部规范老化研究队列中，我们测量了670名老年男性（年龄范围50 - 98岁）的胫骨（n = 670）和髌骨（n = 672）骨铅以及807名老年男性的血铅。基于使用手绘样本的方法创建了一个震颤评分。ALAD基因型被分为是否为ALAD-2携带者。我们使用对年龄、教育程度、吸烟和饮酒量进行调整的线性回归来估计铅生物标志物与震颤评分之间的关联。
在未调整的分析中，所有铅生物标志物的五分位数与震颤评分之间存在微弱关联（p值<0.13），但在调整模型中这种关联并未持续存在。年龄是震颤最强的预测因素。在年龄低于中位数（68.9岁）的人群中，震颤随血铅显著增加（p = 0.03），但这种模式在骨铅方面并不明显。我们未发现ALAD基因的影响，也未发现骨铅与震颤评分随时间变化之间的关联。
我们的结果并不强烈支持铅暴露与震颤之间的关联，且表明与累积铅生物标志物无关联，尽管有一些迹象表明血铅可能与我们队列中较年轻男性的震颤有关。
