Department of Environmental Health Engineering, School of Health, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran; Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran; Health Sciences Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Deep Medicine, Oxford Martin School, University of Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, UK.
Mult Scler Relat Disord. 2020 Oct;45:102426. doi: 10.1016/j.msard.2020.102426. Epub 2020 Jul 28.
A wide range of risk factors, from genetic to environmental, have been identified to play role in the etiology of multiple sclerosis. However, the role of trace element remains mostly unknown. We sought to combine all available evidence to assess the association between copper concentration and multiple sclerosis.
This systematic review and meta-analysis was conducted based on PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science were searched since inception till July 2020. Observational studies that assessed copper as exposure in serum, plasma, whole blood, and cerebrospinal fluid were included. Standardized mean differences (SMD), comparing the mean of copper concentration in multiple sclerosis patients versus healthy controls, were considered as the measure of association. The fixed-effect model with inverse variance weighting was used to combine the findings.
Twenty studies inclusive of 797 multiple sclerosis cases and 875 healthy controls were included in the meta-analysis (all case-control studies). The combined SMDs were 1.25 (95% confidence interval [CI] 0.95 to 1.55, number of included studies [n]=4) in plasma, 0.45 (CI 0.22 to 0.68, n=4) in whole blood, 0.19 (CI 0.06 to 0.33, n=12) in blood serum and 1.23 (CI 0.83 to 1.64, n=4) in cerebrospinal fluid.
We found a higher concentration of copper in multiple sclerosis patients than healthy controls. The possible causal nature of the observed associations warrants further investigation with prospective data.
从遗传到环境，许多风险因素已被确定在多发性硬化症的病因学中发挥作用。然而，微量元素的作用在很大程度上仍然未知。我们试图结合所有现有证据来评估铜浓度与多发性硬化症之间的关联。
本系统评价和荟萃分析根据 PRISMA 指南进行。从成立到 2020 年 7 月，我们在 PubMed、Scopus、Embase 和 Web of Science 上进行了搜索。纳入了评估血清、血浆、全血和脑脊液中铜作为暴露的观察性研究。将比较多发性硬化症患者与健康对照者铜浓度平均值的标准化均数差（SMD）视为关联的衡量标准。使用固定效应模型和倒数方差加权来合并研究结果。
荟萃分析纳入了 20 项研究，共包括 797 例多发性硬化症病例和 875 例健康对照者（均为病例对照研究）。合并的 SMDs 分别为血浆中 1.25（95%置信区间 [CI] 0.95 至 1.55，纳入研究数 [n]=4），全血中 0.45（CI 0.22 至 0.68，n=4），血清中 0.19（CI 0.06 至 0.33，n=12）和脑脊液中 1.23（CI 0.83 至 1.64，n=4）。
我们发现多发性硬化症患者的铜浓度高于健康对照者。需要进一步进行前瞻性研究来探讨观察到的关联的潜在因果性质。
