Upregulation of MTOR , RPS6KB1 , and EIF4EBP1 in the whole blood samples of Iranian patients with multiple sclerosis com
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ORIGINAL ARTICLE
Upregulation of MTOR, RPS6KB1, and EIF4EBP1 in the whole blood samples of Iranian patients with multiple sclerosis compared to healthy controls Fahimeh Akbarian 1 & Mohammad Amin Tabatabaiefar 2,3 & Vahid Shaygannejad 4 & Mohammad Mahdi Shahpouri 4 & Negin Badihian 4,5 & Roshanak Sajjadi 2 & Arezou Dabiri 6 & Nazanin Jalilian 7 & Mohammad Reza Noori-Daloii 1 Received: 12 November 2019 / Accepted: 23 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 sexmatched 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. Keywords MTOR . RPS6KB1 . EIF4EBP1 . Multiple sclerosis . Gene expression
Introduction Multiple Sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system (CNS). It causes different degrees of axonal injury and leads to progressive
* Mohammad Reza Noori-Daloii [email protected] 1
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina St., Tehran 14155-6447, Iran
2
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3
Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
neurodegeneration and accumulation of disabilities (Olsson et al. 2017). MS mostly affe
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