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23andme results interpretation

Discussion in 'Genetic Testing and SNPs' started by Pigpen, Aug 7, 2013.

  1. Pigpen

    Pigpen

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    I've been lurking here for a few days, marvelling at the level of understanding that some of you have. I received my 23andme results back a few weeks ago and I have been trying to work out what they mean ever since. I ran my results through GeneticGenie and livewello.

    By way of some background info I carried out the 23andme test off the back of a just in range (but very low) B12 blood test result, a high off the chart folate test (even though I don't supplement or eat foods fortified with folic acid) and a slightly high out of range homocysteine level. I have Hashimotos disease and my mum has Parkinson's disease and has also had blood clots.

    My results are as follows:

    Homozygous: COMT V158M, COMT, H62H, MAO-A R297R

    Heterozygous: VDR Bsm, VDR Taq, MTHFR c677T, MTHFR 03p39p, MTHFR A1298c, MTR A2756G, MTRR A66G, BHMT 08, CBS A360A, SHMT1 C1420T.

    All of the others are -/-

    To be honest, I don't know where to start or where to look for info and wondered if anyone here can help me?
  2. Pigpen

    Pigpen

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    I should add that my doctor has dismissed my very low B12 as irrelevant because it is in range at 253ng/L (range 220-700) and said that he didn't understand what a high homocysteine level meant but to to worry about it because it was only just out of range at 15.5 umol/l (range 0-15). My serum folate level was >20 ug/l (range 2.6 -17.3). I can't see me being able to get much help from my GP.
  3. Valentijn

    Valentijn Activity Level: 3

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    Your COMT and MAOA are the slow versions, so you aren't using up methyl groups quickly in breaking them down. Hence you might not tolerate an excess of methyl groups being added via vitamins and other supplements.

    Your VDR Bsm/Taq is also a bit slow, so you might not be using up much methyl groups creating those, again potentially limiting how much methyl- supplementation you can handle.

    MTHFR C677T, when combined with MTHFR A1298C, indicates that methylfolate is being produced at about 30% of the normal rate. There's also a list of other relevant MTHFR variants at http://forums.phoenixrising.me/index.php?threads/interesting-mthfr-variations.24543/ which can contribute to folate problems. MTHFR P39P can also have a bit of an impact. Hence methylfolate supplementation is probably required. These problems can also cause elevated homocysteine.

    MTR and MTRR can cause a bit of a problem with elevated homocysteine, and can be helped with B12 supplementation. Due to the VDR, COMT, and MAOA problems, you might not be able to tolerate methylB12, so hydroxoB12 would be a safer version to try.

    BHMT-08 can also elevate homocysteine a bit.

    SHMT1 can aggravate the MTHFR issues. Methylfolate and folinic acid may help.

    CBS C699T is reported backwards by Yasko. The slower version is the riskier one, which is what you have. It can result in elevated homocysteine, which can be helped with B6.

    SUMMARY:
    You almost certainly need methylfolate. Is it possible that the folate test was looking at folic acid as well as (or instead of) methylfolate? HydroxoB12 may also be helpful, as well as B6 and folinic acid. If you have trouble with methylfolate, folinic acid might be a useful substitute.
  4. Pigpen

    Pigpen

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    Thanks for your very speedy reply Valentijn. So lots of things that could be causing the high homocysteine then! At least they seem to have a common solution. I've no idea about whether the serum folate test looked at folic acid but the high level is a bit of a mystery to me and your suggestion does make sense.
  5. Pigpen

    Pigpen

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    I just wanted to also say that I am really appreciative of your help. It's a really generous thing you are doing :)
    ukxmrv and Valentijn like this.
  6. Valentijn

    Valentijn Activity Level: 3

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    On a related note, you might need to avoid sources of artificial folic acid. It's added to a lot of grain products - most breads, cereals, etc.
  7. Crux

    Crux Senior Member

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    Hi Pigpen;
    Well, I hope the doctor will bother to educate himself about the dangers of low B12, elevated homocysteine, and elevated folate.

    It may be the that B12 deficiency has blocked, or trapped the folate from being used to keep the homocysteine in check.

    I also hope that the doc will treat this serious condition with loading doses of B12 injections until you feel better, then, continue to treat you with however much you need, whenever you need it.

    There is information about neurological damage occurring in patients with midrange to even high levels of B12. There's also alot of info about the implications of elevated homocysteine. Here's a link about low B12, elevated homocysteine, and elevated folate, causing cognitive impairment.

    http://www.pnas.org/content/104/50/19995.full
  8. Pigpen

    Pigpen

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    Fortunately I'm gluten free so I manage to avoid most items that are fortified with folic acid already.

    It's extremely unlikely that my GP will bother to educate himself. I've already had to pay privately to get the active B12 and homocysteine tests because the NHS wouldn't pay. I did manage to persuade my GP to refer me to a neurologist (but only if i paid privately) because I have a history of intermittent numbness and pins and needles. I raised the issue of B12 and he wouldn't entertain that as a possible cause at all (even though I knew that to be complete rubbish). So I'm left in my current situation with a low B12 and high homocysteine level with a family history of blood clots that no-one thinks is important! I hate the UK medical system :( I guess my next step is to write to my GP. If I put my concerns in writing and ask for a copy to be placed on my file, they might take things a little more seriously!
    Valentijn likes this.
  9. Pigpen

    Pigpen

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    Thank you for the linked study Crux, it is very informative and I will reference it in the letter I write to my GP. I just don't understand why my GP won't give me B12 shots, after all it's not like they are expensive is it?

    If I was to press my GP for a referral to a specialist (you never know, a miracle might happen!) which type of specialist would look at these sorts of issues? Would it be a haematologist?
  10. Crux

    Crux Senior Member

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    Hi Pigpen;

    Some people have found neurologists to be helpful, as they should be when there are neuro symptoms. ( It surprises me that there are so many who don't have an understanding of B12 def.) Some folks have found haematologists, and others have been lucky with GP's.

    I understand the difficulty finding good treatment in the UK, because I lurk in at the Pernicious Anaemia Society.
    http://www.pernicious-anaemia-society.org/phpbb/

    They suggest going private if one can't find a good doc. Some members have taken to ordering their own products from websites, such as goldpharma.com.

    There are great folks at PAS as well as here. Many of their members don't have PA, but some unknown B12 def. etiology. Most seem to have folate and iron deficiency.

    I tested negative for PA, but I struggle with having elevated folate. ( don't have high homocysteine ) I've found it helps to take high dosages of sublinguals, but I may have to switch to injections. ( My GP will only prescribe cyano,so I'm going to have to find another too.)

    I hope you can find a good doc, nearby.
  11. caledonia

    caledonia

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    I think Valentijn and I are actually going to mostly agree on this interpretation. Valentijn has done her own independent research, and I'm using Yasko's interpretations, so sometimes we disagree on certain points.

    You have two First Priority mutations, SHMT and CBS. For the SHMT, take folinic acid. SHMT is one of the "leaky gut" genes, so it may be a good idea to do some gut testing first, especially if you have multiple food sensitivities, and/or have a high need for potassium or magnesium, especially after you start methylation supps. You'll have to stop and address that before continuing.

    The CBS is the minor one, so chances are it won't cause you any trouble. If you try to start methylation supps, but start getting an anxiety/stress reaction, this is CBS. You'll have to stop and address that before going on.

    You have MTHFR C699T and A1298C, which is the more serious mutation. So you'll likely need methylfolate supplementation. The high folate showing up on the testing is likely "folic acid", which is circulating around in your bloodstream and not absorbing. This is supposed to be a risk for cancer, so it would be good to get that fixed. You should strictly avoid all supps with "folic acid" and all foods fortified with "folic acid" - grains being the main culprit.

    The MTR/MTRR will affect B12 intake and recycling, which is actually showing up as a low B12 test. The range is set too low, so even though it's "in range", it's too low. Minimum level should be at least 500. Heck, mine is showing up 800, and I still have many signs and symptoms of B12 deficiency. So it's almost better to go by signs and symptoms, and take the B12 test with a grain of salt.

    With your COMT and VDR combo, Yasko suggests hydroxycobalamin and adenosylcobalamin, and avoiding methylcobalamin. Otherwise, you could be prone to mood swings.

    You have one BHMT. Ordinarily a bit of TMG might be indicated, but with your COMT status, you should skip it as it's a methyl donor (TMG = tri methyl glycine). You can also do phosphatidyl choline or phosphatidyl serine for this pathway. With only one SNP though, you may be fine without it.

    As far as the B6 Valentijn is mentioning - yes, you probably have the green light to try this. People with an expressed CBS, especially the worse one, C699T, need to limit B6 to 20-25mg.

    Work through the process, doing one thing at a time in order, and completing it before moving onto the next step. Start one supp at a time and note your reaction to it good or bad in a symptom journal. You may need to start with very small doses and gradually build up to a "normal" dose. Do all this stuff cautiously to avoid adverse reactions.

    One more point, have some nicotinic acid form of niacin on hand before you start, in case you get things cranking too fast. This will shut down methlylation quickly and save you from a possibly lengthy period of adverse symptoms. 50-100mg every 4 hours until symptoms subside.

    Check out all the links in my signature.

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