23andme TRPM3 SNPs for CFS - Griffiths Research

Discussion in 'Mast Cell and Histamine' started by Remy, May 3, 2017.

  1. Remy

    Remy Administrator

  2. Remy

    Remy Administrator

    Holy crap, I have almost all of these (for once!).

    rs4738202 A/G, A risk allele
    rs655207 G/T, G risk allele
    rs1160742, G/G, G risk allele
    rs1328153 A/G, G risk allele
    rs3763619, G/G, G risk allele

    Where is that menstrual cramp medicine they talk about, Ponstan? Can we buy that in the US?
  3. JustinCEO

    JustinCEO New Member

    Hi two questions:

    1. Can you link the research you pulled this from?

    2. Is this something where you have to use some external thing to analyze the 23andme raw data?

    Thank you! :D
  4. Remy

    Remy Administrator


    No, you can look up the SNPs in the raw data on the 23andme site directly. Do you know how to do that?
  5. JustinCEO

    JustinCEO New Member

    Thanks for the link!

    I actually just recently ordered my 23andme kit so I don't have my data yet. Just wanted to know what to expect. Good to hear I can look stuff up directly on the 23andme site!
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  6. Issie

    Issie Well-Known Member

    I'm positIve on all 5 also. Now for some other testing.

    I'm looking into calcium channels with P/Q and N calcium channel receptor antibodies, NMDA receptor antibodies, ACHR receptor antibodies. And Muscarinic and A1 and A2 Adrenergic Antibodies. Have orders, just have to go get them done.
    Are any of these doable with our 23&me? I wasn't able to find snps to help here. @Remy

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  7. Remy

    Remy Administrator

    I'm not aware of anything on 23andme that helps with those. I had the standard blood tests done as well (all neg).

    Sorry to hear you're in the club too! :)
  8. Issie

    Issie Well-Known Member

    @Remy did you do any other testing of TRMP3, other than knowing positive alleles on these snps?
  9. Issie

    Issie Well-Known Member

    I'm finding pregnenolone to be beneficial a few times a week. It activates this. Wonder if it helps it to work better? May also explain why GastroCrom has been such a help. It has a mild calcium channel blocking affect. If calcium isn't going into cells properly with this dysfunction - maybe why this helps. Wonder where the connection with MCAS comes in? Tramadol also helps me and is a mild calcium channel blocker. This dysfunction also affects glutamate function and Tramadol also works on NMDA function. More research to do......
  10. Issie

    Issie Well-Known Member

    Here's a whole lot of research. Appears it could be connected to MCAS and potentially POTS as it affects endothelial function and vasodilation.


  11. Remy

    Remy Administrator

    I'm totally confused by this research, at the moment, to be honest.

    I had it backwards in my head that the channels were increased, not reduced as it clearly states, and that intracellular calcium was thus high. High intracellular calcium is a hallmark feature of MCAS which is probably why calcium channel blockers like verapamil can prove useful (and Gastrocrom as well, to some extent).

    But I'm completely confused...Vickery says in her blog post that mefenamic acid is an activator of the TRPM3 channel. But it's not. It's a nearly complete inhibitor. Yet she reports that the Griffiths team are reporting some amount of success using that drug to block the channel, regardless? And that is apparently the supposed recommendation by the researchers?

    Pregnenolone is a strong activator. I can't seem to tolerate it much at all lately. But the articles I read seem to indicate that the activation happens at super-physiological doses, not the doses seen in the body. And that makes some sense, because pregnenolone certainly has a function as a neurosteroid and hormone precursor that would at least seem to be more important than being a calcium channel activator.

    So I'm scratching my head a bit, at the moment, trying to figure out what it all means and if/how it all ties together.
  12. Issie

    Issie Well-Known Member

    Maybe it comes in with what it needs to do in different places in the body. Since it appears to affect all the cells in one way or another - it could be up regulated and down regulated in certain places. Maybe it's equilibrium (per se) is what is off kilter. I have found that upping my acetylcholine has been an amazing affect for me. I take pregnenolone only a few times a week. But GastroCrom (despite my efforts to stop using it) has proven necessary at least once a day if not twice. Tramadol usually once a day, sometimes twice. So I think there is more at play here. I'm trying to learn and sort it myself, I'm trying to educate myself on it. Keep the info coming as you sort it. I like the deeper, science.

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  13. Issie

    Issie Well-Known Member

    @Remy, did you do blood test on the other antibodies I listed above or a different test? You said you were negative on all of them.

  14. Remy

    Remy Administrator

    Yes, a blood test for those other antibodies. I was only positive for GAD65.
  15. Issie

    Issie Well-Known Member

    I just had another POTS friend check her markers and she was only positive on one marker. Her illness came on all of a sudden and mine has been more lifelong. May indicate why the extreme subset differences. Probably not all CFS is genetic - they don't have it completely figured out. But for those who it may be genetic - they may get the science to say thus and so. For us - it's not likely we will get a complete "cure". But for those with an all of a sudden manifestation - maybe there will be one. It is possible though for us to manipulate and tweak our genetics and create a positive epigenetic response. It's just trying to figure out how.
  16. Remy

    Remy Administrator

    The other weird thing is that it sounds like activating these TRPM3 channels increases the secretion of insulin from pancreatic cells.

    Well, I've had elevated insulin out of proportion to my sugar-free ketogenic diet for a long time and it seems like overactive TRPM3 channels could provide a mechanism for this extra insulin.

    I feel like I'm missing something obvious and its making me nuts! :)
  17. Issie

    Issie Well-Known Member

    @Cort did you check yours from your 23&me raw data?

  18. Issie

    Issie Well-Known Member

  19. Lissa

    Lissa Well-Known Member

    Hmmmm I had looked at this a while back, but didn't know what to make of it. I have variations of all of them listed. (These are in the same order as the chart. I didn't include the actual snp's / rs#'s.)

    The only full "match" was the TRPC4 - GG. So what does that mean I wonder? Greek to me....
    I was presuming the indicators would be genes that exactly matched what was listed above?

    MECFS Genes.PNG
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  20. Issie

    Issie Well-Known Member

    I'm not sure what it all means. I had all 5 markers on this. I'm to see my endocrinology doc soon and I'll ask her. It may not be in her field. My primary didn't have a clue. He said I should see a geneticist. He also changed his mind on the orders for the other test. He is retiring and really doesn't have time to learn about this. It's all so complex. Hoping either the endocrinology doc or my neurological doc will run them. If I just have the results - I think I can figure it out. I think we need these other test I mentioned above to figure out which channel receptors are off. We may have autoimmune things happening and testing antibodies here would be helpful. Then.......we will need to figure out what to do if there is that response happening. If someone gets these test before me, please post your findings.

    @Remy there have been several show positive on GAD with POTS. I have been saying forever - there is some sort of dysfunction with glutamate channels and GABA formation. Yet those tend to paradox with GABA supplementation. Probably some sort of cycle conversion issue - like methylation at this channel. Since there is such a tie in with glutamate and dopamine - there may be an issue there too. There are several "types/receptors" of dopamine and seems it was D2 I was researching years ago. Long time ago and I need more choline (brain fog). LOL - working on that. :)

    Last edited: May 16, 2017
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