Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
National Clinical Research Center for Geriatric, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, 610041, China.
Transl Neurodegener. 2021 Jan 8;10(1):3. doi: 10.1186/s40035-020-00228-9.
Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06-0.21], p = 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12-78.73], p < 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52-4.05], p < 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90-127.67], p < 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = - 2.42, 95% CI [- 3.93, - 0.90], p = 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02-1.88], p = 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.
越来越多的证据表明，肌萎缩侧索硬化症（ALS）的病理变化不仅局限于中枢神经系统，还发生在外周循环系统中。在这里，我们基于 PubMed、EMBASE、EBSCO 和 CNKI 数据库进行了一项荟萃分析，以找出与能量代谢、铁稳态和肌肉损伤相关的生物化学指标，这些指标在 ALS 患者中发生改变，并与 ALS 表型相关。该荟萃分析共纳入了 46 项研究，涵盖了 17 种生物化学指标，共涉及 5454 名 ALS 患者和 7986 名对照者。其中 4 项指标，包括空腹血糖水平（加权均数差 [WMD] = 0.13，95%CI [0.06-0.21]，p = 0.001）、血清铁蛋白水平（WMD = 63.42，95%CI [48.12-78.73]，p < 0.001）、转铁蛋白饱和度系数水平（WMD = 2.79，95%CI [1.52-4.05]，p < 0.001）和肌酸激酶水平（WMD = 80.29，95%CI [32.90-127.67]，p < 0.001），在 ALS 患者中明显升高，而总铁结合能力（WMD = -2.42，95%CI [-3.93，-0.90]，p = 0.002）在 ALS 患者中明显低于对照组。相比之下，其余 12 种候选物在 ALS 患者与对照组之间未显示出明显差异。此外，合并危险比（HR）显示，血清铁蛋白水平升高的 ALS 患者的生存时间明显缩短（HR = 1.38，95%CI [1.02-1.88]，p = 0.039）。这些发现表明，能量代谢异常和铁稳态失调参与了 ALS 的发病机制。此外，血清铁蛋白水平与 ALS 患者的总生存期呈负相关。
