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DNA Methylation Modifications Associated with CFS

Discussion in 'Latest ME/CFS Research' started by Sushi, Aug 12, 2014.

  1. Sushi

    Sushi Senior Member Albuquerque

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    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104757
     
    August59, osisposis, NK17 and 13 others like this.
  2. adreno

    adreno PR activist

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    Rich Vank would have enjoyed seeing this.
     
  3. Helen

    Helen Senior Member

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    Thanks @Sushi and agree @adreno . Finally methylation and CFS was studied. Many interesting results.
     
    PennyIA likes this.
  4. Simon

    Simon

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    It's an interesting approach, but note the tiny sample size of just 12 patients and 12 controls
    As the authors acknowledge, this is a cross-sectional study and a longitudinal study (following patients over time, preferably from before they got ill) would be needed to demonstrate a causal relationship.

    IT would have been nice to see more emphasis in the paper on the need for much bigger studies to confirm these findings. It's a start, but we shouldn't get too excited - hopefully the kind of large-scale replication that's needed to confirm these findings will follow soon.
     
    MeSci, Nielk, Sushi and 3 others like this.
  5. Countrygirl

    Countrygirl Senior Member

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    I have just stumbled across this and given my track record for double posting someone will probably tell me that there are already at least three threads discussing it, so I will start :bang-head: now to save time later. :ill: Just in case you haven't already debated it to death I will risk posting it now.

    http://solvecfs.org/breaking-news-chemical-changes-in-immune-cell-dna-from-mecfs-patients/

     
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  6. Helen

    Helen Senior Member

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    @Simon I think you are right about the need for further studies of different kinds, but could we definitely say that n=12 (with matched controls) are too few for drawing any conclusions without having evaluated the inclusion criterias, studied parameters and the choosen statistical method-s ? And maybe a causal relationship never will be confirmed, only a connection - that would be of value to know about too.
     
    SOC likes this.
  7. Bob

    Bob

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    Dolphin likes this.
  8. Valentijn

    Valentijn Senior Member

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    To clarify, this study isn't looking at the prevalence of the genes involved in the methylation cycle (MTHFR, MTRR, BHMT, etc). Rather it's looking at how methylated various genes are. Some are hypermethylated and some are hypomethylated, which would seem to suggest that the problem is in the regulation of the methylation cycle from an outside factor, rather than a strictly genetic issue in those methylation genes themselves.

    Hypermethylated genes: ATG7 BCL10 CD83 FCER2 HLA-H IL19 IL1RL1 LAIR1 TNFSF13B TREM2
    Hypomethylated genes: CD3D CD3E CD3G CD96 FASLG HLA-E ICOS LAX1 LCK LY9

    Maybe this would also mean that supplements and vitamins encouraging methylation might be somewhat helpful for ME/CFS patients, regardless of methylation cycle mutations?
     
    picante, PeterPositive, Sushi and 9 others like this.
  9. DanME

    DanME Senior Member

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    Interesting study. Though the sample and matched control sizes (n=12) are quite small, the patients were carefully selected out of a bigger sample (n=231).

    Volunteers with HIV and HepC were excluded. They selected specifically 12 white female subjects, 52 years or younger, non-obese, with no previous consumption of immunmodulators and only with a sudden viral onset. Furthermore, PEM > 24h, cognitive impairment, a low vitality, low social and/or physical functioning were required.

    The authors themselfs say, though the sample size for this study was small, it was carefully selected and likely representative of sudden onset CFS. I cannot say anything about their statistical analyses (maybe we have an expert around?).

    They found different DNA Methylation in overall 826 genes in four clusters, cellular processes, positive metabolic regulation, kinase activity and mostly in the the immune response. The majority were hypermethylated (> 60%), so inactivated in comparison to controls.

    In my understanding this study has nothing to do with RichvanK's work. Methylation of the DNA activates or inactivates certain gens and their expression in relation to other bodily processes (like autoimmunity) and environmental factors (like an infection or stress). It is not about the methylation process itself.

    Here some quotes, I found interesting.

    "Differentially methylated genes related to immune cell regulation showed an increased proportion of hypomethylated CpG sites among CFS patients, particularly in promoters and in gene regulatory elements."

    "Hypomethylated CpG sites were significantly enriched in promoters and gene regulatory elements of genes related to immune signaling. It is possible that these immune genes may show increased transcript abundance or increased transcriptional potential, at least among the CFS group selected in this study, as promoter hypomethylation is generally associated with an increase in gene expression."

    "Nevertheless, our data provide evidence that epigenetic variation in CFS may be distinct, at least in part, from related disorders with an immunological component. For example, epigenomic analysis of whole blood in fibromyalgia (FM) patients indicated differential methylation in genes associated with structural and nervous system development and neuron differentiation [72]."

    "Although the immune system showed most changes in DNA methylation, we also found an enrichment in gene sets linked to cellular components, kinase activity, and positive metabolic activity, supporting previous data indicating differences in the expression of genes associated with cellular metabolism and oxidative stress in PBMCs from CFS patients [48,51,52]."

    "The results of this study do not indicate whether these observed epigenetic differences are a cause or a consequence of CFS. However, we provide evidence suggesting a potential role for epigenetic alterations in the pathophysiology of CFS."

    I would like to see the same study before and after excersise. :)
     
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  10. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    this is quite interesting, seems to support the idea that immunological abnormalities are present in CFS and could help pinpoint exactly which they are. Also could provide good disease markers. Exiting...
     
  11. Countrygirl

    Countrygirl Senior Member

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  12. Bob

    Bob

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    Countrygirl likes this.
  13. Sushi

    Sushi Senior Member Albuquerque

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    Threads merged

    @Countrygirl, the one you found is a layman's version, so it is a good addition.
     
  14. Countrygirl

    Countrygirl Senior Member

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    Ahhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhh!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!:bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::bang-head::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill::ill:[/quote]


    Edited to say that if anyone is completely bewildered by my apparently bizarre response above and is tempted to question my mental health status :nervous: this is what can happen when two threads are merged.
     
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  15. RYO

    RYO Senior Member

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    My understanding is that we can describe phenotype expression when certain genes become methylated. However, we don't understand what triggered that process (environmental toxins, diet, viral insult) nor do we understand how to reprogram methylation process.

    I am not ruling out that dietary changes or supplements may have some effect but I personally have yet to find a supplement combination to alter disease state.

    I did try fasting for 2 1/2 days. It resulted in mild improvement in intensity of my leg pains. I found fasting difficult. I would not suggest fasting to patients with POTS, low body weight, renal insufficiency or those on multiple medications.

    My personal theory is that for many of us, the viral illness is what "pushes us over the methylation cliff". Wouldn't it be ironic if someone found a way to use a viral vector to fix methylation alterations in ME/CFS.

    Thanks to the author of this thread. Hopefully more research will continue in this area.
     
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  16. Little Bluestem

    Little Bluestem All Good Things Must Come to an End

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    Add hypoglycemia to that.
     
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  17. ukxmrv

    ukxmrv Senior Member

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    Is this important at all?

    "DNA methylation suppresses the expression of endogenous retroviral genes and other harmful stretches of DNA that have been incorporated into the host genome over time. "

    http://en.wikipedia.org/wiki/DNA_methylation
     
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  18. RYO

    RYO Senior Member

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    Yes, DNA methylation suppresses the expression of genes. But as previous comments mention, some areas appear hypomethylated.

    What I would like to know is how a severe viral illness potentially affects long term intracellular function. Does virus alter methylation of genetic sequences that alter immune, mitochondrial, or function of membrane channels. Is it a "hit and run" phenomenon or are there residual viral proteins that linger and alter cellular function long term.
     
  19. lansbergen

    lansbergen Senior Member

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    The cell danger response will go on and on as long as the danger is not eliminated.

    An article
    http://www.sciencedirect.com/science/article/pii/S1567724913002390
     
    Last edited: Aug 15, 2014
    osisposis likes this.
  20. RYO

    RYO Senior Member

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    I reached out to Robert K. Naviaux, MD, PhD. Unfortunately, he didn't think he could help but sent me copy of his paper.

    I am currently ruling out metabolic myopathy with Dr Dwight Koeberl.

    In the meantime, I am trying to achieve "mitocellular hormesis" through diet, mito cocktail, limited exercise, and intermittent fasting. I have yet to find alusive "reboot" button. I suspect biologic systems much more complicated. Studying and taking care of patients with sepsis syndrome is a good example.
     

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