Cellular exocytosis gene (EXOC6/6B): a potential molecular link for the susceptibility and mortality of COVID-19 in diabetic patients

  1. Mahmood Yaseen Hachim
  2. Ibrahim Yaseen Hachim
  3. Saba Al Heialy
  4. Jalal Taneera
  5. Nabil sulaiman

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Abstract

Diabetes is one of the most critical comorbidities linked to an increased risk of severe complications in the current coronavirus disease 2019 (COVID-19) pandemic. A better molecular understanding of COVID-19 in people with type diabetes mellitus (T2D) is mandatory, especially in countries with a high rate of T2D, such as the United Arab Emirates (UAE). Identification of the cellular and molecular mechanisms that make T2D patients prone to aggressive course of the disease can help in the discovery of novel biomarkers and therapeutic targets to improve our response to the disease pandemic. Herein, we employed a system genetics approach to explore potential genomic, transcriptomic alterations in genes specific to lung and pancreas tissues, affected by SARS-CoV-2 infection, and study their association with susceptibility to T2D in Emirati patients. Our results identified the Exocyst complex component, 6 ( EXOC6/6B ) gene (a component for docks insulin granules to the plasma membrane) with documented INDEL in 3 of 4 whole genome sequenced Emirati diabetic patients. Publically available transcriptomic data showed that lung infected with SARS-CoV-2 showed significantly lower expression of EXOC6/6B compared to healthy lungs.

In conclusion, our data suggest that EXOC6/6B might be an important molecular link between dysfunctional pancreatic islets and ciliated lung epithelium that makes diabetic patients more susceptible to severe SARS-COV-2 complication.

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    SciScore for 10.1101/2020.06.25.170936: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Ethics Committee of Sharjah University and the Ministry of Health Research Ethics Committee (R.E.C. number MOHAP/DXB/SUBC/No.14/2017).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Impact of SARS-COV-2 infection on genes involved in insulin secretion in hPSC-derived pancreatic organoid derange: To confirm the link between T2D and COVID-19, a transcriptomics dataset (GSE151803) of SARS-CoV-2 infected hPSC-derived pancreatic organoids[16] were retrieved from Geo Omnibus dataset https://www.ncbi.nlm.nih.gov/geo/.
    Geo Omnibus
    suggested: None
    The bioinformatics analysis was carried out by first aligning the data using the B.W.A. alignment algorithm, followed by sequence filtering using SAMtools.
    SAMtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    Identification of common genes expressed by lung and pancreas: Publicly available tissue gene expression dataset (GTEx) was explored by BioJubies to compare the differential expressed genes of 427 healthy lung samples with 248 healthy pancreases (Figure 1).
    BioJubies
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.06.25.170936v1 on bioRxiv