CREAGEN Research Center of Environmental, Genetic and Nutritional Epidemiology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Metallomics. 2020 May 27;12(5):668-681. doi: 10.1039/d0mt00051e.
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by a loss of function of motor neurons. The etiology of this disorder is still largely unknown. Gene-environment interaction arises as a possible key factor in the development of amyotrophic lateral sclerosis. We assessed the levels of trace metals, copper (Cu), iron (Fe), and manganese (Mn), of 9 amyotrophic lateral sclerosis cases and 40 controls by measuring their content in cerebrospinal fluid. The following trace element species were quantified using ion chromatography-inductively coupled plasma mass spectrometry: univalent copper (Cu-I), divalent Cu (Cu-II), divalent Fe (Fe-II), trivalent Fe (Fe-III), divalent Mn (Mn-II), trivalent Mn (Mn-III), and also unidentified Mn species (Mn-unknown) were present in some samples. When computing the relative risks for amyotrophic lateral sclerosis through an unconditional logistic regression model, we observed a weak and imprecise positive association for iron (Fe III, adjusted odds ratio 1.48, 95% CI 0.46-4.76) and manganese (total-Mn and Mn-II; adjusted odds ratio 1.11, 95% CI 0.74-1.67, and 1.13, 95% CI 0.79-1.61, respectively). Increased risk for copper was found both in the crude analysis (odds ratio 1.14, 95% CI 0.99-1.31) and in multivariable analysis after adjusting for sex, age, and year of storage (1.09, 95% CI 0.90-1.32). Our results suggest a possible positive association between Cu and genetic amyotrophic lateral sclerosis, while they give little indication of involvement of Fe and Mn in disease, though some correlations found also for these elements deserve further investigation.
肌萎缩侧索硬化症是一种进行性神经退行性疾病，其特征是运动神经元功能丧失。这种疾病的病因在很大程度上仍然未知。基因-环境相互作用被认为是肌萎缩侧索硬化症发展的一个可能的关键因素。我们通过测量脑脊液中的含量来评估 9 例肌萎缩侧索硬化症病例和 40 例对照者的痕量金属铜 (Cu)、铁 (Fe) 和锰 (Mn) 的水平。使用离子色谱-电感耦合等离子体质谱法定量测定以下痕量元素种类：一价铜 (Cu-I)、二价铜 (Cu-II)、二价铁 (Fe-II)、三价铁 (Fe-III)、二价锰 (Mn-II)、三价锰 (Mn-III)，以及一些样品中存在的未鉴定锰物种 (Mn-unknown)。在使用无条件逻辑回归模型计算肌萎缩侧索硬化症的相对风险时，我们观察到铁 (Fe-III，调整后的优势比 1.48，95%置信区间 0.46-4.76) 和锰 (总-Mn 和 Mn-II；调整后的优势比 1.11，95%置信区间 0.74-1.67 和 1.13，95%置信区间 0.79-1.61) 呈微弱而不精确的正相关。在未调整分析中发现铜的风险增加 (比值比 1.14，95%置信区间 0.99-1.31)，在调整性别、年龄和储存年份后进行多变量分析时也发现铜的风险增加 (比值比 1.09，95%置信区间 0.90-1.32)。我们的结果表明 Cu 与遗传肌萎缩侧索硬化症之间可能存在正相关，而 Fe 和 Mn 与疾病的关系则几乎没有迹象，但对于这些元素的一些相关性也需要进一步研究。
