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Clarification on gene testing and gene expression

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by PeterPositive, Oct 28, 2013.

  1. PeterPositive

    PeterPositive Senior Member

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    Hello,
    this might have been asked a lot, but a search in the forums didn't return anything.

    Supposing one's genetic test, say 23andme, contains a number of methylation related polymorphisms (e.g. MTHFR mutations etc...) how does one know if they are expressed?

    I might be very well missing a basic piece of the picture, but it is my understanding that mutations of the MTHFR genes is quite widespread but not everyone suffers from the related health issues because it is expressed (epigentically) in a fraction of the population,

    Sorry for possibly asking a dumb question, but I am relatively new to the issue and I feel like I don't have the full picture.

    Thanks in advance :)
    Waverunner likes this.
  2. caledonia

    caledonia

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    Amy Yasko's book has a list of tests and symptoms for the various SNPs to determine if they're expressed. Chapter 6. There's a link to her book in my signature.
  3. Beyond

    Beyond 10% of discount in iHerb!--> PEZ915

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    If you are sick they are expressed, all or at least some of them, is quite simple.
  4. Critterina

    Critterina Senior Member

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    I agree with lab tests as being a good indicator of whether they are expressed; I just don't agree with all the Yasko philosophy/interpretation. I would suggest you get a practitioner you can work with. Easier said than done, of course.
    Valentijn likes this.
  5. PeterPositive

    PeterPositive Senior Member

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    Thanks for your replies.
    @Critterina: yes it is easier done than said, indeed :) Over here in Italy there's very few doctors that I know of that have enough experience with this kinds of problems.

    My ND is actually the one that brought up the methylation issue almost immediately and suggested to get started with active forms of B vitamins. The other doctors I spoke with just noticed the high Hcy values and prescribed injections of CyanoCbl and Calcium folinate. When I mentioned sublingual coenzymated Bs they rolled their eyes as if I was talking about the tooth fairy :D

    Fortunately this board can provide some direct experiences and directions, which is very valuables. So thank you very much for your time and patience.
    Valentijn and Critterina like this.
  6. Helen

    Helen Senior Member

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    Hi PeterPositive,

    There is a labpanel called Methylation Panel from Health Diagnostics that is appropriate for evaluating the outcome of gene defects in the methylation cycle. There should be facts and help for interpretation here posted by richvank who had a great experience of this test from people with ME/CFS.

    You can get the test from the Netherlands or from U.S. When I last ordered it there was a small but important difference between the two panels. I choose the U.S. lab.

    A high homocysteine is a probable marker for B12 and/or folate deficiency. So is also the methylmalonic acid test. But there is so far no absolute valid B12 test.

    I wouldn´t take cyanoCbl as it is thought to be toxic (the cyano part of it). It can be detoxified by HydroxyCbl according to some source. Serg1942 here wrote about his problem with toxicity. HydroxyCbl has to be methylated to the bioactive MethylCbl so if the methylation is impaired it might not work. You then have to take MethylCbl.

    Calcium folinate has to be "processed" to L-5-methyltetrahydrofolate and if this doesn´t work for any reason you will not get the right amount of the bioactive MTHF. 200 mcg of each was the recommendation from richvank, but there are other protocols here too (Freddd´s).

    Best,

    Helen
  7. PeterPositive

    PeterPositive Senior Member

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    Thanks Helen,
    I will look into the methylation panel, sounds like an interesting "companion" for the genetic test.

    Yep, I didn't take cyanoCbl but I did take quite a bit of folic acid. The Hcy did go down from 98 to ~14 and now I am stuck there even though my serum values of f.acid and B12 are both over the scale.

    Personally I can handle 500-600mcg of Methyl-B12. At 1000mcg I start feeling mild histamine related side effects or jittery. Adenosyl B12 doesn't do that and I've read a bit about the difference between the two.

    cheers
  8. Critterina

    Critterina Senior Member

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    Yes, I am so thankful for the help I've received here. I have been able to modify my diet to low histamines, so I don't have the breathing problems I did. And I have also been able to identify a missed diagnosis, so now I can pursue a diagnosis and treatment. It may end up saving my life.:thumbsup:
  9. Valentijn

    Valentijn Activity Level: 3

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    I think too much is made of "the gene is expressed". While some things can up- and down-regulate genes, the vast majority are going to be "expressed" all of the time.

    For example, MTHFR C677T can cause serious folate problems. There's not +/+ people who are "expressed" and +/+ people who are "not expressed". While some MTHFR C677T people might be able to maintain adequate folate levels through diet or supplementation, that is a matter of compensating for the expression of the gene - it's not doing anything to change how the gene functions or is "expressed".

    As a group, the people with +/+ have low folate levels compared to -/- people, which is the natural expression of their version of that gene for each group. While there are some genes which are very much controlled by other genes, etc, they are rather in the minority. Hence I would assume a gene is basically always functioning based on its composition, rather than making attributions to an unproven expressor.

    Plus I rather dislike using "expression" as a fallback to explain why certain interpretations (Yasko's, for example) are often incorrect. It's too often used as an excuse to avoid a scientific explanation for a theory, generally because there isn't a scientific explanation for the theory at all.
    Helen likes this.
  10. PeterPositive

    PeterPositive Senior Member

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    Thanks, Valentijn.
    For example where I live we have Sicily as being among the top places in the world where the MTHFR mutation is very "popular", and yet the amount of people that are sick is not increased compared to other places. For example, take in consideration miscarriages which seem to be heavily dependent on Folate levels.

    Of course, I might be making it too easy since the variables at play are quite a lot but I was pondering on the differences between those that get sick and those who don't.

    I am not sure if I fully understand, I probably need to learn a lot more before I can get the bigger picture here. Would you care to expand on this? I thought the idea of epigentics was quite well founded, or maybe I misunderstand.

    Cheers
  11. Valentijn

    Valentijn Activity Level: 3

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    So unless they are eating a ton of veggies, they are probably somewhat deficient in folate. This doesn't mean they will automatically be sick or show any signs of disease. A lot of people are folate deficient without any obvious signs, until certain conditions occur, such as illness or pregnancy.
    I'm not saying that identical genes can't be expressed differently. But I think it's a bad idea to assume that it's a major factor in cases where there's no evidence supporting it.

    Earlier I mentioned Yasko's theories as being problematic in this context. To be more specific, she has some completely unfounded theories about very minor CBS mutations. Because they are quite wrong, many people wonder why they are not having the expected symptoms. And the answer usually seems to be "well it just isn't being expressed." There's never been any indication that something can cause very minor and beneficial mutations to suddenly become drastically harmful, yet "expression" is relied upon as the explanation.

    So while I don't doubt that expression happens, I think it's a bit silly to assert that it explains something, when no such changes in expression have ever proven or even indicated for that gene or SNP. I prefer to think that a gene operates as it operates, unless there's some indication otherwise. It's illogical to assume something is happening which has never been shown to happen for that SNP, such as changed expression due to some mysterious and undescribed mechanism. And it's often used to dodge scientific rationality, which makes it particularly annoying to me :p
  12. PeterPositive

    PeterPositive Senior Member

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    Valentijn,
    thanks for your insight, it makes sense. I am only partially familiar with Yasko's theories, I have followed some of the videos and skimmed her online resources. There's quite a lot to process and also not everything is probably relevant to what I am looking for.

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