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Please help me analyze my genetic results

Discussion in 'Genetic Testing and SNPs' started by plasticperson32, Apr 24, 2013.

  1. plasticperson32


    Hello everyone my name is Pat and this might me my first post on this forum but I have been a long time lurker. It was this forum that motivated me to take a dna test from 23andme so that i can trully understand my metabolic problems and not just speculate based of off symptoms.

    I show classic undermethylator and pyrolouric symptoms. I have already addresses my pyroluria symptoms with a zinc/vitb 6 based supplement regimen. I could help anyone in the area of pyroluria just PM me. (vitb6/zinc isn't the only thing in my regimen). If you want to check if you have pyroluria the SNP responsible is Rs4654748 on gene NBPF3; positive for any T base pairs.

    I uploaded my results from genetic genie so all gene mutation are easy to interpret. My results revealed that I have big problems in the BHMT pathway and MAO-A. I want to focus on addressing the bhmt deficits considering not much can be done to help the MAO-A deficits (correct me if i'm wrong).

    From what I have researched so far theyre is a slew of vitamin supplements and rna nucleotide supplements I can consume to dampen the undermethylator symptoms and facilitate the bhmt pathway.

    First off, the vitamins supplements that ive read that could potentially help include TMG, DMG, NADH, METHIONINE/SAMe. However, im a little skeptical of these supplements, specifically TMG. Around 3 months ago, prior to me taking the dna test, I started dosing about 500 mg of TMG every morning and it resulted in an alleviation of my undermethylator symptoms while simultaneously causing weight gain and excessive urination. I understand why the TMG cured the methylation symptoms. But I still don't understand the weight gain and excessive urination.

    I have a hypothesis that the weight gain and excessive urination was caused by the TMG remethylating too much homocysteine. Therefore, not enough homocysteine was being metabolized and entering the CBS pathway causing the problems. If anyone could shed any light on the wieght gain and excessive urintation that would be great.

    I want to take TMG/DMG/NADH/METHIONINE supplements but I worry about them causing adverse reactions in the concentration of BHMT. For example, If one takes DMG, bhmt is down regulated resulting in a reduction of the endogenous BHMT production/TMG metabolism.

    I think if one takes these supplements they should balance them with the compounds present before and after the BHMT enzyme so one will have higher levels of TMG/DMG/METHIONINE and no reduction in BHMT caused by down regulation due too excess DMG. What does everyone think on this?

    Secondly, as for the RNA nucleotide supplements I am very clueless. I don't understand they're mechanism of action, side effects, or basically anything. If anyone could add they're anecdotal report with they're experience and maybe some links to websites with information i would greatly appreciate it!!!!!:thumbsup:

    In advance thanks for any help and I will hopefully help you all. Ive been researching metabolism for some time now and have acquired information that could be useful on this forum. Ask any questions!

    Screen Shot 2013-04-24 at 6.14.53 PM.png
  2. plasticperson32


    alright thats a good point thanks for the help
  3. Philla


    Hi Plasticperson32,

    being in the same boat myself I am not sure if I can help you out on this one, but your panel does seem to have some similarities with mine (see my lengthy post for more info). I also share the same undermethylator traits (per Pfeiffer/Walsh criteriae). This part also correspond very well to our charts (COMT + / - and VDR taq + / -). We also seem to share MAO + ('The warrior gene'), which is causing major fluctuations in serotonin.(lol.. I can attest this) From what I have read, Yasko points out that this could further predispose for bacterial overload, due to more tryptophan floating around. Not 100 % sure here though.

    On your TMG experience:
    From what I know, Yasko puts huge emphasis on 'order of healing', when intervening in the methylation pathway.
    First SHMT/ACAT, then CBS -> MTHFR -> MTR/MTRR -> BHMT -> MAO A -> SUOX -> NOS -> VDR.

    Although you are only heterozygous CBS A 360, your defective BHMT pathways will probably burden the CBS pathway a lot, only creating even more sulfur and ammonia for your heterozygous MTHFR A1298 to clean up. Ammonia detox depleting BH4 (which then depletes mood and neurotransmitters..) could be the result.

    Remember also that your MTRR status will affect the MTHFR A1298 negatively and needs some methylB12 to bypass. Although I do not follow Yasko blindly, I think her recent emphasis on low dose lithium (orotate) is interesting. Without sufficient Lithium, the MTRR will not use B12 efficiently, hence supplementing MethylB12 will dump Lithium excessively.

    For further elaboration check her 'Your simplified road map to health' and video posted on her FB. Personally I am going to do a lithium trial, since I have massive need for B12 but turn hypomanic and hyperexcitatory after a period of supplementation.

    As for the RNA supplements I haven't come across any impressive testimonials from people using them. I have seen many people online critisize Yasko for her extented use of them in her protocols, many also debunk them since they (seemingly) are all equal, in terms of contents. So after all, this is not where I would empty my pocket...

    Possible strategy:
    Support the 'short route' partly in the beginning (Phosphatidylcholine, Serine, etc), then priotitize CBS (lower ammonia, sulfates, eradicadysbiosis) for so to embark on 'the long route' with small dose Lithium for B12 retention, then small dose Methylb12, methylfolate and (possibly) TMG.

    As you can see, I am a novice in this field like many others, but being my own 'lab-rat' I want to take prudent steps, not inducing any major problems.

    Take care and good luck! (Pardon my english, it gets sloppy some times - esp. when short of methylB12 :) Give me a note if anything needs clarification.. And just for curiosity, I suspected pyroluria long ago, and I do have a lot of the traits attributed to it. I did however check the SNP in 23andme raw data folder and it was "CC".. Interesting after all ..
  4. Lynn_M

    Lynn_M Senior Member

    Western Nebraska
    According to dbSNP, about 30% of European ethnicity people have the rs4654748 CC allele of the ALPL NBPF3 gene. CC is associated with a 2.90 ng/ml lowered Vit B6 blood concentration. Since the major of the population, depending on ethnicity, have the T allele, I have a hard time believing it confers risk for pyroluria. I did a lot of reading on rs4654748 allele today, because I have the CC risk variant. I have seen no reference to any association between rs4654748 and pyroluria, nor could I find one when I searched on those two keywords.

    Plasticperson32, could you share some references for your statement that the T allele of rs4654748 is responsible for pyroluria?
    Valentijn likes this.
  5. Valentijn

    Valentijn Senior Member

    This happens quite a lot ... researchers look at a million SNPs, and one or two abnormalities pop up. The effect size (if it actually exists after corrections) is usually tiny. Yet it ends up getting blamed for disease, even though 30% of the population has it without any problems.
  6. shoponl


    re: SNP rs4654748, with "T" risk allele for pyroluria

    I think this is a red herring. In our family, we had:
    CC = positive for pyroluria
    CC = negative
    CT = borderline
    CT = negative

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