■多发性硬化症(MS)是中枢神经系统最常见的慢性炎性疾病。目前,MS的病理机制尚未完全了解,但是研究表明,铁代谢紊乱可能与MS的发病和临床表现有关。
■该研究利用公开可用的数据库和生物信息学技术进行基因表达数据分析,包括差异表达分析,加权相关网络分析,基因富集分析,并构建Logistic回归模型。随后,孟德尔随机化用于评估不同铁代谢标志物与MS之间的因果关系。
■这项研究确定了IREB2,LAMP2,ISCU,ATP6V1G1,ATP13A2和SKP1作为与多发性硬化症(MS)和铁代谢相关的基因,建立其对MS的多基因诊断价值,AUC为0.83。此外,孟德尔随机化分析显示转铁蛋白饱和度与MS之间存在潜在的因果关系(p=2.22E-02;OR95CI=0.86(0.75,0.98)),以及血清转铁蛋白和MS(p=2.18E-04;OR95CI=1.22(1.10,1.36))。
■本研究通过整合的生物信息学分析和孟德尔随机化方法,全面探索了铁代谢与MS之间的关系。这些发现为进一步研究铁代谢紊乱在MS发病机制中的作用提供了重要见解,为MS的治疗提供了重要的理论支持。
Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS.
The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS.
This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)).
This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.