Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina St., Tehran, 14155-6447, Iran.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Metab Brain Dis. 2020 Dec;35(8):1309-1316. doi: 10.1007/s11011-020-00590-7. Epub 2020 Aug 18.
Various genetic and epigenetic mechanisms have been suggested to play roles as the underlying pathophysiology of Multiple Sclerosis (MS). Changes in different parts of the mTOR signaling pathway are among the potential suggested mechanisms based on the specific roles of this pathway in CNS. MTOR, RPS6KB1, and EIFEBP1 genes are among important genes in the mTOR pathway, responsible for the proper function of acting proteins in this signaling pathway. This study aimed to investigate the relative expression levels of these genes in the blood samples of relapsing-remitting MS (RRMS) patients compared to healthy controls. In this case-control study blood samples were collected from 30 newly diagnosed RRMS patients and 30 age and sex-matched healthy controls. mRNA level of MTOR, RPS6KB1, and EIFEBP1 genes were assessed using Real-Time PCR. The expression of MTOR, RPS6KB1, and EIF4EBP1 genes was up regulated in MS patients compared to healthy controls (p < 0.001 for all mentioned genes). Considering gender differences, expression of the mentioned genes was increased among female patients (all P < 0.001). However, no statistically significant changes were observed among male patients. Based on the receiver operating characteristic, MTOR gene had the highest diagnostic value followed by EIF4EBP1 and RPS6KB1 genes in differentiating RRMS patients from controls. In conclusion, we found the simultaneous upregulation of MTOR, RPS6KB1, and EIF4EBP1 genes among RRMS patients. MTOR showed to have the highest diagnostic value compared to other 2 genes in differentiating RRMS patients. Further studies evaluating the importance of these findings from pharmacological and prognostic perspectives are necessary.
多种遗传和表观遗传机制被认为在多发性硬化症（MS）的发病机制中起作用。基于该途径在中枢神经系统中的特定作用，mTOR 信号通路的不同部分的变化是潜在的建议机制之一。MTOR、RPS6KB1 和 EIFEBP1 基因是 mTOR 途径中的重要基因，负责该信号通路中作用蛋白的正常功能。本研究旨在调查这些基因在复发缓解型多发性硬化症（RRMS）患者血液样本中的相对表达水平与健康对照组相比。在这项病例对照研究中，从 30 名新诊断的 RRMS 患者和 30 名年龄和性别匹配的健康对照者中采集了血液样本。使用实时 PCR 评估 MTOR、RPS6KB1 和 EIFEBP1 基因的 mRNA 水平。与健康对照组相比，MS 患者的 MTOR、RPS6KB1 和 EIF4EBP1 基因表达上调（所有提到的基因均 P<0.001）。考虑到性别差异，在女性患者中提到的基因表达增加（所有 P<0.001）。然而，在男性患者中未观察到统计学上的显著变化。根据受试者工作特征，MTOR 基因在区分 RRMS 患者和对照组方面具有最高的诊断价值，其次是 EIF4EBP1 和 RPS6KB1 基因。总之，我们发现 RRMS 患者中 MTOR、RPS6KB1 和 EIF4EBP1 基因同时上调。与其他 2 个基因相比，MTOR 在区分 RRMS 患者方面具有最高的诊断价值。需要进一步研究从药理学和预后角度评估这些发现的重要性。
