The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
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Prone to hypochondria, and scared of my methylation results. Should I be?

Discussion in 'Genetic Testing and SNPs' started by adonisofnumenor, Jun 11, 2015.

  1. adonisofnumenor

    adonisofnumenor

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    Hello everyone! Thank you in advance for your time, your prior post, and your advice. Basically, I am ok, in the early mornings, literally die in the afternoon, and without a nap I can barely function until bed. I used to be a heavy drinker, but I don't anymore. That has helped, and I also mediate now. That has been a lifesaver. I take many supplements, trying to find something to give me some energy, something to allow me to focus and some days I can. But most days, I can't. After doing the methyl test on genetic genie, I am left with only more questions. I have so many mutations ( 6 homozygous (+/+) mutations and 11 heterozygous (+/-) mutations. :( . Some of these seem to work against each other, and overall, I am honestly a little scared by it. Mostly I am confused. Below are my abysmal results. Any advice?

    heterozygous
    MTRR H595Y rs10380 CT +/-
    MTRR K350A rs162036 AG +/-
    BHMT-04 rs617219 AC +/-
    BHMT-08 rs651852 CT +/-
    MTRR R415T rs2287780 CT +/-

    homozygous
    MTHFR C677T rs1801133 AA +/+
    MAO A R297R rs6323 T +/+
    AHCY-01 rs819147 CC +/+
    AHCY-02 rs819134 GG +/+
    AHCY-19 rs819171 CC +/+
    CBS C699T rs234706 AA +/+


    The few, but proud absent mutations.

    ACAT1-02 rs3741049 GG -/-
    MTHFR 03 P39P rs2066470 GG -/-
    MTHFR A1298C rs1801131 TT -/-
    MTRR A66G rs1801394 AA -/-
    MTRR A664A rs1802059 GG -/-
    BHMT-02 rs567754 CC -/-
    CBS A360A rs1801181 GG -/-
    CBS N212N rs2298758 GG -/-
    SHMT1 C1420T rs1979277 GG -/-
     
  2. Critterina

    Critterina Senior Member

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    Arizona, USA
    Hi @adonisofnumenor ,

    SNPs are information. Should you be scared of information? It doesn't change what is, only what you know. And we've all heard the saying a little knowledge is a dangerous thing. Be scared if you enjoy it, otherwise don't bother. So, what I write next is opinion, not medical expertise.

    In my opinion, you have a few significant mutations, most of the rest you can probably ignore. The most significant are the two homozygous mutations MTHFR C677T and MAO-A.

    The MTHFR slows the conversion of folinic acid to methylfolate. You can probably get around this deficiency by using methylfolate supplements. How much to take and how quickly to increase your dose is a whole other matter.

    Most people with this MTHFR SNP end up having high homocysteine levels, since their methylfolate is low, and that's one of the primary methyl donors in converting homocysteine back to methionine. But since you have several ACHY SNPs, and that is what helps form homocysteine, it would be interesting to see just what your homocysteine and methionine levels are. I have no idea what else to do to help your ACHY function better, sorry. But don't worry, I'm sure you can find plenty of opinions.

    The MAO A mutation slows down the breakdown of serotonin. You'd think that this means you'd have plenty of serotonin and be happier than other people, not at all prone to depression. Well, there are other things going on, much too complicated for me to explain or maybe even fully understand, but that doesn't seem to be the case very frequently. I think that it means that you might have strong reactions to supplements that are methyl donors, but I think it's more than just the MAO A that leads to that, so you might not. Anyways, with supplements the wisdom chant is "Start Low and Go Slow."

    The heterozygous are pretty minor MTRR SNPs and two BHMTs. The BHMT 08 is the more significant, and it also helps recycle homocysteine into methionine, but instead of needing methylfolate as a substrate, it needs trimethylglycine (TMG). I would not recommend that you supplement TMG unless you are trying to nudge your lab results or symptoms.

    Some people in this forum say that if you're going to supplement methylfolate, you may need to supplement some form of B12. That's because methylB12 is part of the catalyst that takes a homocysteine molecule and a methylfolate molecule and turns them into another folate molecule (tetrahydrofolate) and methionine. Otherwise, the theory goes, that you can accumulate too much methylfolate and not be able to use it. I'm not totally bought in to that whole theory, but it's worth mentioning. My not believing in something doesn't mean it's not true.

    So, you can probably (in my opinion) benefit from taking methylfolate; not something to be scared of. I guess the only thing to be scared of, is more something to be informed of. If you're planning to have children, and the mother has MTHFR C677T, the form of the prenatal vitamins will be important, particularly the methylfolate in them. You don't want her taking folic acid.

    There's a lot to understand with the SNPs, and even if you don't have brain fog, it's really hard to put it all together. Ask your doctor about the MTHFR that you have, and if s/he doesn't know, ask for a referral to someone who does. Get some guidance, if you can, from them about taking methylfolate - how much and what to look out for. You can find a lot of info on this website, too, but nothing here is a good substitute for a doctor who knows you.

    Best of health to you!

    Crit.
     
  3. Valentijn

    Valentijn WE ARE KINA

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    @adonisofnumenor - The good news is that most of your +/+ variations probably aren't doing much of anything. CBS C699T +/+ is a mild and beneficial upregulation, and there's no research anywhere indicating that those AHCY SNPs ever have any impact at all.

    MAOA isn't really part of methylation, but (theoretically) might impact how people respond to high doses of vitamins containing methyl-donors, such as methyfolate or methylB12.

    So really the only issue you have is MTHFR C677T +/+. This reduces gene function to about 30% of the optimum. But due to MTHFR variations being extremely common, "normal" gene function in the general population is a bit under 70% of optimal anyhow. The biggest known impact of moderate down-regulation in that gene is increased risk of birth defects for mothers who have that variation. But according to the relevant research, those risks are completely off-set by either taking a normal dose of folate or eating a diet with a decent amount of vegetables.

    If still concerned, having homocysteine levels tested from time to time could show if your slow MTHFR is resulting in actual problems.
     
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  4. adonisofnumenor

    adonisofnumenor

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    Thank you so much! Your answer, as well as @Valentijn have made me feel so much better. I put an order in earlier this morning for the methylfolate, and I am due for a blood test in July. Thank G-d my wife does not have the same mutations. I'll update as I learn more. Again, thank you so much and I wish you both the best of health.

    Sincerely,



    P.S.

    For anyone reading this that share the mutations above, and have a history of depression or anger. This is what I had learned up to this point.
    Sam-e made me feel manic and overall bad , methlycobalamin b-12 seems to help, saunas are wonderful, pray/mediate, alcohol should be enjoyed in moderation, although I excel at lifting weights (anaerobic), I feel better when I run/jog/bike/row (aerobic/cardio).
     
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  5. whodathunkit

    whodathunkit Senior Member

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    @adonisofnumenor: probably you know this but in case you need a reminder :) : diet is huge in getting that anger and depression under control. I've been battling mood dysfunction my entire life, and the only time I've ever made any substantial, non-transient headway is when I'm eating a good clean diet. Meds and supplements just can't consistently do for my mood what a good diet does. Diet plus the right supplements = I don't behave like a ping-pong ball in an empty concrete room in response to life's stressors. Close enough to normalcy to kiss. Thankfully I can eat pretty much anything I want, but it has to be real food, not processed. Also can't overdo any one thing (have a tendency towards mono-eating just because of the convenience of it). Healthy fats are absolutely essential, and I've recently learned that saturated fat should be the main fat (at least for me), plus small daily supplementation with omega-3's (I like CLO). No omega-6 except what naturally occurs in the real food I eat (that is, no omega-6 oils).

    I just got my genetics tested and no surprise I am homozygous for MAOA (rs6323). Based on my history I was expecting some problems with this snp and would have been very surprised if it didn't show up. Long live the Worriers/Warriors/Psychopaths! :D
     
    Last edited: Jun 15, 2015
    adonisofnumenor likes this.

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