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Preprint: The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in [ME/CFS].., 2021, Malato et al

Discussion in 'ME/CFS research' started by Andy, Mar 31, 2021.

  1. Andy

    Andy Committee Member

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    Full title: The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput genetic, epigenetic, and gene expression studies

    Abstract

    Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) show specific epigenetic and gene expression signatures of the disease. However, it is unknown whether these signatures in ME/CFS include abnormal levels of the human angiotensin-converting enzyme ACE and ACE2, the latter being the main receptor described for host-cell invasion by SARS-CoV-2.

    To investigate that, we first reviewed published case-control genome-wide association studies based on single nucleotide polymorphism data, case-control epigenome-wide association studies based on DNA methylation data, and case-control gene expression studies based on microarray data. From these published studies, we did not find any evidence for a difference between patients with ME/CFS and healthy controls in terms of genetic variation, DNA methylation, and gene expression levels of ACE and ACE2.

    In line with this evidence, the analysis of a new data set on the ACE/ACE2 gene expression in peripheral blood mononuclear cells did not find any differences between a female cohort of 37 patients and 34 age-matched healthy controls.

    Future studies should be conducted to extend this investigation to other potential receptors used by SARS-CoV-2. These studies will help researchers and clinicians to better assess the health risk imposed by this virus when infecting patients with this debilitating disease.

    https://www.medrxiv.org/content/10.1101/2021.03.23.21254175v1.full-text

    Line breaks added for easier reading.
     
    Last edited by a moderator: Mar 31, 2021
    Wonko, Snow Leopard, Milo and 13 others like this.
  2. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    I'm not sure why they thought there would be a difference, but better to know than not know, right?
     
    SNT Gatchaman, Simon M, FMMM1 and 2 others like this.
  3. Hutan

    Hutan Moderator Staff Member

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    I think they were checking out an old finding:
    I was interested in this, as the two times my level of ACE was tested, it was slightly high.

    To me, it seems that the authors tried to do a solid study. They reviewed previous studies covering ACE in ME/CFS, appearing to understand good practice in the gene expression evaluation techniques, and also to understand the importance of well-characterised patients (e.g. they excluded studies where participants self-reported ME/CFS, required Fukuda or CCC diagnosis).

    This was an interesting comment:
     
    Kitty likes this.
  4. Hutan

    Hutan Moderator Staff Member

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    There are some good comments on how these studies could be done better e.g.this one on making data publicly available:
     
    SNT Gatchaman, Wyva and Kitty like this.
  5. Hutan

    Hutan Moderator Staff Member

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    This was an interesting paragraph that concludes
    "Therefore, perturbations of the normal levels of DPP4 would appear to be a hallmark of ME/CFS pathogenesis."

     
    SNT Gatchaman, Kitty and Wonko like this.
  6. Andy

    Andy Committee Member

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  7. mango

    mango Senior Member (Voting Rights)

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  8. Hutan

    Hutan Moderator Staff Member

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    That new link takes you to:

    The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data

    Abstract

    People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Given that this reporting agrees with different immunological abnormalities and altered gene expression profiles observed in the disease, we aimed at answering whether the expression of the human angiotensin-converting enzyme 2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in these patients. In particular, a low expression of ACE2 could be indicative of a high risk of developing COVID-19.

    We then performed a meta-analysis of public data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found that patients with ME/CFS have decreased methylation levels of four CpG probes in the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another probe in the promoter region of the ACE2 gene (cg08559914). We also found a decreased expression of ACE2 but not of ACE in patients when compared to healthy controls.

    Accordingly, in newly collected data, there was evidence for a significant higher proportion of samples with an ACE2 expression below the limit of detection in patients than healthy controls. Altogether, patients with ME/CFS can be at a higher COVID-19 risk and, if so, they should be considered a priority group for vaccination by public health authorities. To further support this conclusion, similar research is recommended for other human cell entry receptors and cell types, namely, those cells targeted by the virus.​


    _______
    It looks like this is a different paper, or a significant re-write. The abstract in the first post says:
    I don't know what's going on, but the findings of the two papers are different.
     
    Amw66, Michelle, Snow Leopard and 3 others like this.

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