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Input on 23andme results?

Discussion in 'Genetic Testing and SNPs' started by chloe5763, Aug 14, 2013.

  1. chloe5763


    Hi there!

    I am trying to work my way through this wealth of information trying to help our DD who is 7 and suffering from a myriad of symptoms including extreme fatigue, OCD like behaviors and rages. It looks like she definitely has Methylation issues but I am getting confused with the other issues that would conflict with supplements. She does test for Lyme exposure and we do have a LLMD that we will see today (second visit) but he does not seem too interested in the 23andme results so I think I have to figure at least part of this out on my own....Here is her data....any help and advice would be greatly appreciated!!

    Gene & Variation rsID Alleles Result
    COMT V158M rs4680 AG +/-
    COMT H62H rs4633 CT +/-
    COMT P199P rs769224 GG -/-
    VDR Bsm rs1544410 CC -/-
    VDR Taq rs731236 AA +/+
    VDR Fok-I not found n/a n/a
    MAO A R297R rs6323 GT +/-
    ACAT1-02 rs3741049 AA +/+
    MTHFR C677T rs1801133 AA +/+
    MTHFR 03 P39P rs2066470 GG -/-
    MTHFR A1298C rs1801131 TT -/-
    MTR A2756G rs1805087 AA -/-
    MTRR A66G rs1801394 AA -/-
    MTRR H595Y rs10380 CT +/-
    MTRR K350A rs162036 AG +/-
    MTRR R415T rs2287780 CT +/-
    MTRR S257T not found n/a n/a
    MTRR A664A rs1802059 GG -/-
    BHMT-01 not found n/a n/a
    BHMT-02 rs567754 TT +/+
    BHMT-04 rs617219 CC +/+
    BHMT-08 rs651852 TT +/+
    AHCY-01 rs819147 TT -/-
    AHCY-02 rs819134 AA -/-
    AHCY-19 rs819171 TT -/-
    CBS C699T rs234706 GG -/-
    CBS A360A rs1801181 AG +/-
    CBS N212N rs2298758 GG -/-
    SUOX S370S not found n/a n/a
    NOS3 D298E not found n/a n/a
    SHMT1 C1420T rs1979277 AA +/+
  2. Valentijn

    Valentijn Activity Level: 3

    I'm not home now and don't have access to most of my notes, but this result sticks out - it can cause folate production to be reduced to 30% of normal, hence supplementing methylfolate (not folic acid) is probably needed.

    You also might want to check her results against the list at http://forums.phoenixrising.me/index.php?threads/interesting-mthfr-variations.24543/ to see if she has additional mutations, since they can interact with C677T to make things even worse.
  3. Critterina

    Critterina Senior Member

    Arizona, USA
    Besides the C677T, this one stuck out to me. Not only will the C677T cause reduced conversion folinic acid to methylfolate, she may be low on folinic acid, which is made by the SHMT1 enzyme. I'll defer to Valentijn on this (and mostly everything :)) , but I would think this would further lower her naturally-made methylfolate.

    chloe5763, I am not implying that she'll need to supplement with folinic acid; because she is MTHFR A1298C -/- she can make it from methylfolate. In fact, when this happens, it also reactivates the biopterin enzyme (changes it from BH2 to BH4) which is the enzyme that's used to make serotonin and dopamine. Those chemicals are likely involved in her mood/behavioral issues. Fatigue has a lot of sources.

    What are her SHMT2 results? rs12319666 and rs34095989.
  4. caledonia


    Cincinnati, OH, USA
    First I would run a Nutreval test especially because you're dealing with a child who will have trouble reporting symptoms to you. The Nutreval is a combination of several tests. This will give you an overall picture and a direction to go in. See the Nutreval interpretation guide link in my signature.

    She has several "leaky gut" genes - SHMT, ACAT and the BHMTs can add to this. So if the Nutreval shows gut issues, do more gut testing with the Metametrix GI Effects and Doctors Data CSA tests. Then treat the gut with a 4R gut program. You should also support SHMT and ACAT while doing this to make sure it "takes". I'm not sure when you can stop support for them, maybe when you get the whole cycle working. That would be a good question to ask on the Yasko forum.

    CBS is the minor one, but BHMTs can add to this. CBS can also be linked to Lyme. I'm not sure if Lyme makes CBS get expressed even if you don't have SNPs or what the deal is, but I've heard that treating CBS can help Lyme patients get better results. You should do some testing to see if CBS is expressed, then treat for that if it is. You can also go by symptoms, which is having a stress/anxiety reaction when starting methylation supps. Heartfixer has a good summary of what to do for CBS, which I've used successfully with a few modifications.

    You need to complete the first steps before getting into actual methylation or uncomfortable or even dangerous adverse events can occur (speaking from firsthand experience here). She'll need methylfolate for the MTHFR, B12 for the MTRRs, and TMG and some form of phosphatidyl choline for the BHMTs.

    For the B12, her COMT/VDR SNPs aren't that bad - Yasko suggests using all three forms - hydroxy, methyl, and adenosyl, with less methylcobalamin.

    If the Nutreval shows metals, getting rid of gut microbes and restarting methylation will start metal detox. She may or may not have to do a separate metal detox program, but if she does, look into Andrew Cutler's protocol. Other protocols or the incorrect use of ALA (alpha lipoic acid) may drive mercury into the brain, instead of pulling it out like you would want. You can do Doctors Data Urine metal tests to keep track of metal excretion.

    ps. If you determine that you want to treat for Lyme first (take antibiotics), then I would suggesting testing and treating for CBS if necessary along with the Lyme program. Then test the gut and complete a 4R program after you're done with antibiotics.

    Good luck, sounds like a long haul, but definitely doable over time.
    helen1 likes this.
  5. Valentijn

    Valentijn Activity Level: 3

    I've deleted the -/- results, crossed out the results for which there's no research showing that they're at all relevant, and highlighted in orange two SNPs for which Yasko (and geneticgenie) reports the risk backwards of the actual risk.

    Her biggest problem is MTHFR C677T, as was mentioned above. This means her folate production is reduced to 30%. The SHMT1 mutation can amplify the effects of MTHFR C677T, so actual production rates might be even lower. The treatment for this is to take methylfolate.

    The risk for BHMT-08 is reported backwards, so she has the better version of that one.

    CBS C699T risk is reported backwards, thus she has the slower version, which might result in homocysteine accumulating. B6 can help with that.

    There are quite a few slow-ish versions of MTRR, including A664A, which is reported backwards. Hence supplementing with B12 might be helpful.

    MAOA and COMT are the not-fast versions, hence methyl groups might not be getting used up quickly, which could result in 1) reduced tolerance to methyl supplementation, and 2) neurotransmitter imbalance. Hence B12 should probably be supplemented in the form of hydroxoB12 instead of methylB12, and methylfolate supplementation should probably start at a somewhat normal level, rather than a high dose.

    Methylfolate supplementation is probably needed, but watch out for a reaction to the methyl groups. Normal dose is typically 200mcg for a child her age - if going much higher, you should probably talk to a doctor first and/or get her methylfolate (not folic acid) levels tested.

    B12 is also probably helpful, but hydroxoB12 form is probably safer, due to her COMT/MAOA and behavioral problems.

    B6 may also help, especially if there's a homocysteine problem.

    Testing neurotransmitter levels (serotonin, dopamine, norepinephrine, epinephrine) levels may also be useful, due to both the COMT/MAOA and behavioral issues. Glutamate levels also might be worth checking out.
    helen1 likes this.
  6. kday

    kday Senior Member

    CBS C699T, MTRR A664A, BHMT-08 are not reported backwards.

    dbSNP and SNPedia report on the plus strand and 23andMe reports on the minus strand. But when you look at OpenSNP you can see that the risk alleles are correct for those genotyped on illumina chips that report on the minus strand

    MTRR A664A
    12% are AA
    38% are GG
    Risk Allele: A

    CBS C699T
    10% are AA
    47% are GG
    Risk Allele: A

    dbSNP (plus orientation) risk: A
    23andMe (minus orientation) risk: T

    It's hard to see what the "risk" would be on openSNP since there is not much difference on this SNP (1% difference between TT and CC on OpenSNP). However, the risk allele on dbSNP is AA. And for this SNP we can safely flip AA to TT. So T would the the risk.


    Edit:After reading your posts again, maybe I am not clear on what you mean by "reported backwards".
  7. Valentijn

    Valentijn Activity Level: 3

    You seem to be assuming that the rare version is always the riskier one. This is far from being the case.

    To be clear, I'm saying that yasko (and geneticgenie, based on yasko) are reporting the risk backwards. My opinion that they are reporting it backwards is based on reading the actual research.
  8. kday

    kday Senior Member

    Right, many studies and physicians assume high homocysteine = good and low homocysteine = bad. So CBS would be seen as good in some eyes if there isn't any other apparent disease process going on where a CBS upregulation may not be so good (such as Down Syndrome).

    Other studies investigate disease processes that aren't related to our what we are using the data for. So you have to be cautious when grabbing "risks" from these studies because the authors found one variant to be protective against whatever.

    My memory is bad so I can't think of many specific examples, but I know for many detox genes they look at cancer risk. On certain SNPs there is a nearly a 50/50 split on what the risk allele is. Sometimes certain populations show one "risk" while other populations show the "risk" to be the complete opposite. You have to ask yourself, "what is the risk I am looking for and for who". This is why the word risk is not my favorite term.

    If you are saying that low homocysteine from CBS is protective, fine. But protective against what and in what population?

    I know there is controversy between how Yasko interprets CBS or if it really means anything. Some studies show that there isn't much of a a difference in homocysteine with certain CBS SNPs. I've seen people with Autism and CFS with a CBS mutation and Autism show high ammonia and taurine.

    Of course this can be from a different disease process altogether, but Yasko sacrificed her credibility to help people (I think she said something along those lines, but don't have a quote). That's not to say that she can't be completely wrong about some things. But nevertheless, there are some well-researched and important SNPs even if you discount the rest because of lack of research.

    However, despite the uncertainties of genetic testing and how other environmental factors can interfere with functioning of certain enzymes (mutation or not), I think the follow-up functional testing she always recommends can be very useful (if you have a doctor that knows how to read it), but expensive.
  9. Valentijn

    Valentijn Activity Level: 3

    Protective against every population with the possible (and theoretical) exception of Downs Syndrome. There hasn't been any study showing any harm from having the faster version of any CBS SNP. Whereas there are many studies showing increased risk from having the slower versions.
  10. kday

    kday Senior Member

    Fair enough. But the slower versions are much more common when it comes to C699T, and I have trouble seeing why nature wouldn't select the supposed more beneficial or "protective" variant. Of course, nature doesn't always get everything right, but that's not really my point.

    I guess my point is that I don't know if the science is right or wrong, and won't make claims either way. But I think it may be fair to say the science could be immature.
  11. Valentijn

    Valentijn Activity Level: 3

    Actually the faster (normal) versions are more common for most CBS SNPs. Of the ones in 23andMe which have sufficient research, only 2 out of 16 have the slower version as being more common. And those 2 don't involve missense or similar mutations which can cause a change in the structure of the gene, hence are probably having a very small impact in general.

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