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Methylation SNP's - Opinions please?

Discussion in 'Genetic Testing and SNPs' started by MakingProgress, May 4, 2015.

  1. MakingProgress

    MakingProgress

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    Hi everyone - this is the genetic genie methylation report generated from my 23andMe data.

    I'm new to this and would very much appreciate some advice on what this means?

    upload_2015-5-5_12-43-29.png

    Thanks in advance for your help.

    Nick
     
  2. AndyPandy

    AndyPandy Making the most of it

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    @MakingProgress you might like to have a look at the blog on PR called Caledonia's Methylation Links. There you will find a link to SNPs Interpretation Guide which you may find helpful.
     
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  3. MakingProgress

    MakingProgress

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    Thanks Andy - got it.
     
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  4. MakingProgress

    MakingProgress

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    @AndyPandy thanks for the advice. I've been through @caledonia s Methylation links and have a good understanding of what each means individually. Where I'm struggling is understanding the interaction of the SNP's and what this means for me. Any help with that would be great!
     
  5. AndyPandy

    AndyPandy Making the most of it

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    @MakingProgress I am just a beginner in this area. Hopefully someone more knowledgeable will be able to help you out.

    Best wishes, Andy
     
  6. It's helpful to study a methylation cycle diagram, such as the one at Heartfixer. http://www.heartfixer.com/AMRI-Nutrigenomics.htm

    You can start to see how everything is interrelated. Don't worry if it makes your brain explode - this is normal :)
     
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  7. MakingProgress

    MakingProgress

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    Thanks @caledonia - I've been through the heartfixer site and think that the order of issues would be:

    1. AHCY - I'm double homozygous for 2 of the 3 AHCY genes and had a "no call" on the third. I think this is my primary methylation issue as AHCY is the only path for synthesis of Homocysteine (with Adenosine as a by product). As far as i can see this is the only way the body makes Homocysteine and i'm going to be doing that slowly. This would also give me reduced levels of Adenosine which could result in fatigue (I have this) and lowered immunity (i also have this).

    2. CBS - I'm double heterozygous for CBS and this is an upregulation SNP. Usually this is considered a primary issue as it shunts too much Homocysteine through the Ammonia / Sulphation path, but as i'm slow at producing Homocysteine because of the AHCY, the CBS mutation is somewhat mitigated. To the extent that a CBS upregulation is doing this I'm probably pulling BH4 away from neurotransmitter synthesis to break down the excess ammonia. This would mean I'm slow to produce Serotonin and Dopamine (i have depression and have been on anti depressants for 5 years) so that looks possible.

    3. MAOA - I'm homozygous (equivalent) for MAOA297R (and for 3 of the other MAOA SNP's). This would mean i'm very slow to break down Serotonin & Dopamine and one symptom would be a temper (yep!). However - because of the CBS pulling BH4 away from the creation of Serotonin - and I also have SNP's on DDC, VDR and TPH - I'm likely to be slow to produce Dopamine and Serotonin. Hard to interpret this but if i had to, i'd assume that as long as my serotonin and dopamine are in balance, I'm fine, but going either way on either (too much or too little) will be a problem as my ability to increase and reduce both are slow - so mood swings (also tick).

    4. MTHFR C677T - This is needed to complete the conversion of THF to 5-MTHF and I'm slow at doing this. This is needed for 2 things:
    a. Break down Homocysteine, not so much of an issue as the AHCY means i'm slow to produce that and CBS grabs what i do produce, so probably mitigated,
    b. Creation of BH4 as a by product in reverse - more of an issue as BH4 is being taken through the CBS route to break down ammonia. Not mitigated as this probably works with the CBS mutation to reduce my production of neurotransmitters.

    5. COMT & VDR - See the end of comment 3. My ability to make and break down Dopamine & NorEpinephrine are compromised, but probably this is less of an issue than it might be as I'm slow to create these due to a lack of BH4.

    I'd really like someone with more knowledge and experience than me to confirm or correct me on any of the above if possible.
     
  8. Valentijn

    Valentijn Senior Member

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    The Yasko AHCY SNPs aren't known to have an impact at all. So those can be ignored unless and until proven otherwise some day.
    C699T is a beneficial up-regulation, and a very mild one especially when heterozygous. The other Yasko CBS SNPs aren't known to do anything.
    This is a synonymous variation in a coding section, hence I really doubt it's doing anything itself. It might be reflecting a change elsewhere which has an impact, but I'd never assume that based on what other people are claiming about it. It's necessary to read the relevant research yourself, to determine if it even has an impact at all.
    This reduces your MTHFR enzyme activity to about 65% of the ideal functioning. But these are very common mutations, and average enzyme activity in the general population is around 70%. At most, it indicates that you might have some benefit from taking a normal dose of methylfolate (not folic acid) or eating a decent amount of vegetables in your diet.
    COMT variations can have a big impact on gene function, but are 1) all very common, and 2) don't directly result in consistent problems. At any rate, +/- could probably be considered to be the most average and least extreme version.

    The VDR variations listed basically count as one variation, because they almost always go together. Being +/- for both is equivalent to being +/- for one. And it has very little impact when homozygous, so is probably having little or no impact when +/-.
     

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