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Seeking input on my Genetic Genie results

Discussion in 'Genetic Testing and SNPs' started by Hraz, Jan 3, 2014.

  1. Hraz


    I'm new to this forum and recently had Genetic Genie pull my 23andMe results. Below are my Methylation Analysis Results. I have no idea if anything here should raise a red flag. Are there any supplements people would recommend or avoid based on these results? Is there a non-technical book on the subject people could recommend? I appreciate in advance any guidance offered.

    Gene & VariationrsIDAllelesResult
    COMT V158Mrs4680AG+/-
    COMT H62Hrs4633CT+/-
    COMT P199Prs769224GG-/-
    VDR Bsmrs1544410CT+/-
    VDR Taqrs731236AG+/-
    MAO-A R297Rrs6323TT+/+
    MTHFR C677Trs1801133GG-/-
    MTHFR 03 P39Prs2066470GG-/-
    MTHFR A1298Crs1801131GT+/-
    MTR A2756Grs1805087AA-/-
    MTRR A66Grs1801394AA-/-
    MTRR H595Yrs10380TT+/+
    MTRR K350Ars162036GG+/+
    MTRR R415Trs2287780CC-/-
    MTRR A664Ars1802059GG-/-
    CBS C699Trs234706AG+/-
    CBS A360Ars1801181AG+/-
    CBS N212Nrs2298758GG-/-
    SHMT1 C1420Trs1979277AA+/+

    You have 1 heterozygous (yellow) mutation(s). These are generally not as bad as red homozygous mutation, but they may still worth paying attention to. They include:

    • MTHFR A1298C
    Now let's move on to discuss what these MTHFR mutation(s) mean.
    MTHFR A1298C
    MTHFR A1298C is involved in converting 5-methylfolate (5MTHF) to tetrahydrofolate (THF). Unlike MTHFR C677T, the A1298C mutation does not lead to elevated homocysteine levels. This reaction helps generate BH4. BH4 is important for the detoxification of ammonia. The gene is compromised about 70% in MTHFR A1298C (+/+) individuals, and about 30% in people with a heterozygous (+/-) mutation.

    BH4 acts as a rate limiting factor for the production of neurotransmitters and catecholamines including serotonin, melatonin, dopamine, norepinephrine, and epinephrine. A MTHFR A1298C + status may cause a decrease in any of these neurotransmitters or catecholamines. BH4 is also a cofactor in the production of nitric oxide. A dysfunctional BH4 enzyme may lead to mental/emotional and/or physical symptoms. Mercury, lead, and aluminum may act as a drain on BH4.

    Here are your homozygous mutations as indicated in your SNP gene table above (not including MTHFR):

    • MAO-A R297R
    • MTRR H595Y
    • MTRR K350A
    • BHMT-08
    Here are your heterozygous mutations as indicated in your SNP gene table above (not including MTHFR):

    • COMT V158M
    • COMT H62H
    • VDR Bsm
    • VDR Taq
    • BHMT-02
    • BHMT-04
    • AHCY-01
    • AHCY-02
    • AHCY-19
    • CBS C699T
    • CBS A360A
  2. Critterina

    Critterina Senior Member

    Arizona, USA
    I am no expert, but I can offer a first opinion: nothing here I would supplement for without additional lab results or symptoms. The things I notice:

    BHMT-08 ++ slows down conversion of homocysteine to methionine through that path, but your other path (that uses methylfolate and methylb12) seems like it is absent the mutations that most affect it's activity. So, if you have lab work that shows high homocysteine, you might consider supplementing with TMG. Without the lab result, I wouldn't.

    SHMT ++ may slow down the conversion of folic acid to folinic acid. There is no research that I know of that says this is a problem unless you also have MTHFR C667T, which you don't. There is also no research that I know of that says it isn't, but there are probably other paths to make the conversion. You also get folinic acid from vegetables (leafy greens, I think), so if you have a good diet, you probably are just fine.

    MTHFR A1298C +/- will slow down the "backward" MTHF reaction that as a byproduct make tetrahydrobiopterin (BH4). You still have over 50% activity there, so whether you have symptoms related to that probably depends more on your environment and lifestyle than on your genetics. Symptoms associated with low BH4 can be depression, anxiety, bipolar, autism, OCD, ADHD, etc. In that case, supplementing may help, and you'd supplement with methylfolate, but you might also be sensitive to that, since some of your other SNPs are sometimes associated with sensitivity. If you're already on meds for your symptoms, methylfolate may change your need for them, so proceed with caution and with professional guidance if you can find it.
  3. Hraz


  4. Hraz


    Thanks so much for your reply. The one time I had my homocysteine levels tested they were high. There are a lot of very anxious people in my family, so this is worth further investigation.
  5. Valentijn

    Valentijn Senior Member

    @Hraz :

    MTRR K350A and MTRR H595Y both likely have a significant impact on methylation, as they both increase the risk of elevated homocysteine and associated diseases. K350A has been shown to result in a 3.0 elevated risk factor of spina bifida [1], and H595Y results in elevated homocysteine and decreased levels of MTRR with an effect ratio of 1.45 [2]. It's also possible that the combined effect of the mutations is worse than the cumulative effect of each mutation.

    Because MTRR activity is likely impaired to some extent, B12 might help. Some people have trouble tolerating methylB12, in which case hydroxoB12 might be more tolerable.

  6. Hraz


    Valenijin, thanks for your answer and thanks for the links.

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