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Upregulation of MTOR, RPS6KB1, and EIF4EBP1 in the whole blood samples of Iranian patients with multiple sclerosis compared to healthy controls

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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 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.

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Funding

This research was supported by Tehran University of Medical Sciences & Health Services (Grant number: 31264).

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Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina St., Tehran, 14155-6447, Iran

    Fahimeh Akbarian & Mohammad Reza Noori-Daloii

  2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Amin Tabatabaiefar & Roshanak Sajjadi

  3. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Amin Tabatabaiefar

  4. Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Vahid Shaygannejad, Mohammad Mahdi Shahpouri & Negin Badihian

  5. Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Negin Badihian

  6. Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Arezou Dabiri

  7. Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Nazanin Jalilian

Authors
  1. Fahimeh Akbarian
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  2. Mohammad Amin Tabatabaiefar
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  3. Vahid Shaygannejad
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  4. Mohammad Mahdi Shahpouri
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  5. Negin Badihian
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  6. Roshanak Sajjadi
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  7. Arezou Dabiri
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  8. Nazanin Jalilian
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  9. Mohammad Reza Noori-Daloii
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Corresponding author

Correspondence to Mohammad Reza Noori-Daloii.

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The study was approved by the ethics committee of Tehran University of Medical Sciences (code: IR.TUMS.REC.1395.2718). Informed consent was obtained from all individual participants included in the study. The study was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments.

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Akbarian, F., Tabatabaiefar, M.A., Shaygannejad, V. et al. Upregulation of MTOR, RPS6KB1, and EIF4EBP1 in the whole blood samples of Iranian patients with multiple sclerosis compared to healthy controls. Metab Brain Dis 35, 1309–1316 (2020). https://doi.org/10.1007/s11011-020-00590-7

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  • DOI: https://doi.org/10.1007/s11011-020-00590-7

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