Invest in ME Conference 12: First Class in Every Way
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My 23andME

Discussion in 'Genetic Testing and SNPs' started by Ninan, Apr 2, 2016.

  1. Ninan

    Ninan Senior Member

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    Finally did this. Just got it, suspect it explains some things. Like the fact that I needed enormous amounts of vitamin D not to be deficient. Probably was all my life until two years ago. And my issues with B12.

    Greatful for any insights if you feel like it. :) Methylation_Sida_1.jpg
     
  2. alicec

    alicec Senior Member

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    There's nothing there to be worried about.

    The two VDR results are the normal common alleles. Genetic Genie has followed Yasko in deciding that the common allele of VDR Taq is the risk and so reports it as +/+. Research doesn't support this but in any case, even the risky versions of both alleles have only a small effect.

    This would not be the reason for high need for vit D. (Note these SNPs refer to the vit D receptor, not vit D. In general VDR is not going to affect vit D levels except perhaps if it is really defective and simply can't bind and process vit D which then accumulates in the blood. This would be very rare.)

    The first COMT SNP does slow the enzyme but you are +/- so it would be a small effect. Don't believe the Yasko myth that COMT SNPs mean you can't handle methyl groups. Some people do indeed have problems but it has little to do with COMT.

    The second COMT has little effect.

    MTHFR A1298C has a slight slowing of the enzyme but +/- is very little.

    The MTR SNP does do something. There was controversy about whether it was an upregulation (as claimed by Yasko) or a downregulation. I can't remember the research since it is a SNP I don't have. The competing claims suggest that the effect whatever way it goes is not great.

    Cover yourself by taking some methylB12.

    The MTRR SNP does slow the enzyme. The +/- effect is relatively small, again cover yourself by taking some methylB12.

    The BHMT and CBS SNPs do very little.

    Genetic Genie analyses a very small number of SNPs, based on Yasko's claims which are seriously wanting.

    There are other alternatives which analyse far more genes, eg Promethease and MTHFR Support. You can't just accept what they say and really have to do research of your own to back things up, but they do provide a better place to start and do give links to research.
     
  3. prioris

    prioris Senior Member

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    i erased this post since my query has been obsoleted
     
    Last edited: Apr 4, 2016
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  4. Helen

    Helen Senior Member

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    CYP3A4 has an impact on the metabolism of 50-60 % of all medicins and is very important to keep in mind when choosing drugs. Cortisone, for example, is one of the drugs that isn´t cleared normally with this CYP, and may therefore be taken in too high doses with serious adverse effects.
    One of many sites : http://medicine.iupui.edu/clinpharm/ddis/main-table/

    Wouldn´t it be a good idea to have your own thread?
     
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  5. Sea

    Sea Senior Member

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    It is important not to confuse the effect of a gene (CYP3A4) with the effect of a snp (rs12721627). Much research has to be undertaken to determine what, if any, an individual snp has. It seems this one has some effect but nothing compared to some other snps on this gene.

    Having said that though I am quite certain that the way this is reported is an error. @Valentijn The rarity of this snp is such that I would not expect to find anyone else with it yet I also am GG. It is one of those ambiguous snps that can easily be confused. Is your result in 23andme GG or CC for this snp? @prioris
    GG at 23andme would be a normal result. CC would be the mutation.
     
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  6. Valentijn

    Valentijn The Diabolic Logic

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    Agreed ... it's reported in reverse on dbSNP, but their listing of minor alleles is always in the forward alignment. So near the top of http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs12721627 it can be seen that "MAF/MinorAlleleCount" is 0.0008 for the C allele. 23andMe reports everything in the forward alignment, so C would also be the rare allele there.

    It's also odd that they're listing that SNP as any sort of risk factor at all, since research has shown that it isn't associated with low CYP3A4 protein levels or activity: http://www.ncbi.nlm.nih.gov/pubmed/11875366
     
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  7. Sea

    Sea Senior Member

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    Variations in the FUT2 gene influence vit B12 levels measured in plasma. These 3 snps are in strong linkage disequilibrium, which means they are usually inherited as a set. Their frequency is around 50% so not really going to be making a huge difference.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673801/

    Also rs492602 GG is the allele associated with higher B12 plasma levels so I don't know why they have designated your GG as ++

    I'm sorry prioris, what sticks out to me from your results is that MTHFR.net don't really know what they're doing
     
    Last edited: Apr 3, 2016
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  8. prioris

    prioris Senior Member

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    I don't take any medications. They are toxic to my system. Outside of one day test trials, I have only tried a handful of medications. I stay with natural medicines. Have done for decades. I would prefer to have my own thread but I didn't want to create redundant threads. Plus the title was generic enough.
     
  9. prioris

    prioris Senior Member

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    I think Dr Benjamin Lynch - he is the guru on methylation - influences what genes get flagged on the report on MTHFR. He'd have to tell you why.

    I did get a genetic genie report but it didn't seem useful at all

    Are there any other software to run my 23andme genetics thru
     
  10. prioris

    prioris Senior Member

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    don't know why quote in post got doubled up. oh well.
     
  11. Sea

    Sea Senior Member

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    Promethease is a good one. Their information is based on SNPedia with links to research.

    Double check anything anyone tells you with the actual research papers because there is a lot of misunderstanding and misinformation out there. Most of the people willing to take your money for interpretations have no background in genetics.

    Dr Benjamin Lynch (a natropath) may be seen as the guru on methylation but you'll have to do your own research if you are interested in accuracy
     
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  12. Sea

    Sea Senior Member

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    Also, it would be a good idea to ask a moderator to move your conversation to a new thread. Otherwise ninan is going to get an alert every time someone posts because it's her thread, and if someone wants to respond specifically to you they'll need to quote or tag you @prioris
     
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  13. prioris

    prioris Senior Member

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    if the moderator wants to do that then that's fine. may be more work than it's worth for them and may be a short lived thread anyway.

    In terms of misinformation, I seemed like Yasko's has contradictions. Dr Lynch did point out that there is disagreements on what this or that SNP means. My only interest in the genetics is just allowing me to understand if it can lead to anything practical. I may have to use the tools that Lynch has given and come up with my own protocol thru trial or error. Even b12 can effect me negatively.
     
  14. Ninan

    Ninan Senior Member

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    Detox_Sida_1.jpg Taking back the thread if you don't mind, @prioris ;)

    Thanks for your answer, @alicec ! Explained a lot. I'm using Livewello now, is that ok? Going to check out MTHFR support. My health is really messy now and I need all the clues i can get.

    This is my detox profile btw.
     
  15. mango

    mango Senior Member

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    keeping my fingers crossed for you @Ninan, hoping you'll find all the clues you need :hug:
     
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  16. Ninan

    Ninan Senior Member

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    Thanks @mango Working on it. :)
     
  17. alicec

    alicec Senior Member

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    First Genetic Genie is reporting the CYP2D6 S486T the wrong way round. GG is the normal ancestral allele. BUT this is one of those tricky changes of G to C and the way it is reported depends on the orientation. It needs to be checked very carefully to really determine whether you are wild type or variant.

    Having said that the frequency of minor allele is 0.4012. In other words the variant is very common.

    Even if you have the variant, this in itself doesn't mean much, nor do the other CYP SNPs for which you are +/-.

    Combinations of SNPs can have very marked effects of the activity of the CYP enzymes (all of them, not just 2D6) and working these out can be a nightmare. Here for example is the SNPedia entry for CYP 2D6, listing the SNPs that constitute the various phenotypically defined alleles.

    You need more info than genetic genie provides to work out if you really have any of these alleles (and maybe not even then!).

    I can't remember what LiveWello reports. Promethease makes an attempt to work out the CYP alleles but it is all very confusing.

    The same sort of comment applies to NAT. It is combinations that matter, not individual SNPs. Again I know that Promethease tries to classify you as low, high or intermediate metaboliser based on all your NAT SNPs, don't know about LiveWello.

    The two GSTP1 SNPs definitely slow the enzyme, but the effect with +/- is small. Supplements which stimulate glutathione production might be a good idea.

    The SOD2 A16V definitely does something. +/+ has a 30-40% reduction in activity. This is the manganese dependant version of the enzyme operating in mitochondria. Supplementation with Mn may help to stimulate a sluggish enzyme.
     
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  18. Ninan

    Ninan Senior Member

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    image.jpeg That last part is very interesting, @alicec ! My mitochondria is more or less dead. And my manganese is low. It's 2 AM here, will read again tomorrow.
     
  19. Ninan

    Ninan Senior Member

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    Here's the full MTHFR report if anyone wants to take a look.
     

    Attached Files:

  20. Ninan

    Ninan Senior Member

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    I've been reading a bit about the SOD2 A16V. I have great effect from B12 but it comes only after almost exactly 50 hours. Nothing before that. Could it be the antioxidant effect of B12 that is important to me since I have this mutation? @Hip or @alicec ?
     

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