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Lesson Learned: SNPs and NutrEval

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Jorlev, Jul 13, 2013.

  1. Jorlev

    Jorlev

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    Had my 23andMe done and like most, was concerned with the array of SNPs that were homozygous and heterozygous and what that my mean for my health. Am homozygous for MTHR 1298C and heterozygous for CBS C699T plus several MTRRs, NOS3 and SOD2.

    Was sure that my Sulfate and Ammonia would be high and my BH4 would be low and perhaps my Glutathione as well.

    Well the lesson is this: You can have all the messed up SNPs in the world but you have to find out if they are being expressed. And you won't know that unless you follow up with comprehensive testing.

    I had a NutrEval Plasma, Organix Comprehensive Profile, CDSA, Thyroid and Allergens checked.

    Turns out my Glutathione is very high and Ammonia / Sulfate are quite good. Oddly, I seem to have an IgG Egg reaction that was off the chart high so bye-bye eggs. Biopterin was high so looks like 1298C is not being expressed.

    Some dysbiosis with high 3- Hydrophenylacetic Acid and Benzoic Acid. Anyone with knowledge on these, would love to hear from you.

    Vitamin D moderately low. Isoleucine, Taurine, Succinic Acid - Low

    A-Linolenic low but EPA and DHA high. Wondering if A-linolenic matters since I thought it is only important for it's conversion to EPA / DHA. What else does A-Linolenic do???
    Thoughts on that would be appreciated.

    Creatinine, urea, threonine, asparagine - High

    Mercury in the RED in the lower part of the High range - 0.0049. Wondering if detox is in order?
    Have only 2 really small fillings so I assume this is mostly seafood related.

    Anyone who's really sharp on NutrEval or the ramifications of any of these readings, would greatly appreciate your insights. Read Rich's piece on NutrEval, which was very informative but if anyone knows further your replies would be invaluable.

    Learned must from these test. Please go out and get'em for yourselves!
    helen1, Beyond and Star-Anise like this.
  2. Valentijn

    Valentijn Activity Level: 3

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    Most of the Yasko SNPs have little or no effect on gene function. MTHFR C677T is the exception, and MTHFR A1298C can have bad effects at least when interacting with a heterozygous C677T.

    But for the other SNPs you're getting either no effect or a pretty mild one. Also some risks are reported backwards, and being heterozygous for the Yasko SNPs usually has no effect at all.
  3. joshi81

    joshi81 Senior Member

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    sorry vale but what do you mean by most of the yasko SNP have little or no effect on gene function? do you mean that they are not importan and not predictive on the rate of the function of the gene?
  4. Valentijn

    Valentijn Activity Level: 3

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    Yes. A few are relevant to the gene function, but it looks like 14 of them aren't supported by any research.
  5. joshi81

    joshi81 Senior Member

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    For example...in the panel tha yasko suggests i cannot find the SNP for Glutathione...here in italy is the firs SNP they run and in particular GSTM GSTT GSTP (the gluthathioneS tranferase) and in many of us with CFS we find that we have GSTM1 absent!
    Valentijn likes this.
  6. Valentijn

    Valentijn Activity Level: 3

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    Yes, I think there a lot of SNPs useful to ME patients which are not in the Yasko panel. That is another reason I think 23andMe is a much better buy.
  7. Bluebell

    Bluebell More % Neanderthal than Adreno but less hairy :-D

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    Vale, is there a list somewhere of the SNPs that are useful to ME patients which 23andMe includes?
  8. Valentijn

    Valentijn Activity Level: 3

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    I'm working on it, slowly, amidst too many new health issues and doctor appointments (I really do hate going to the doctor, even when I know I need to and that it can be very helpful :mad:). But like the SNPs in other panels, most are associated with minor changes in gene function, and lack a large sign saying "HERE IS TEH ME!" :D
  9. roxie60

    roxie60 Senior Member

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    what do you mean bu absent? do you mean 'no call' for GSTM1?
  10. August59

    August59 Daughters High School Graduation

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    This what makes me want to wait just a little while longer before I have these done. I believe it would confuse me more than help until I got a good handle on which one means what.
    Little Bluestem likes this.
  11. Valentijn

    Valentijn Activity Level: 3

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    The entire gene, or most of it, can be absent. I have normal GSTM genes, but I'm missing GSTT1.

    It's not super uncommon - 15% of europeans have the GSTT1 missing. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395771/ discusses the effects of a "null" GSTT1, and also mentions GSTM1.
  12. Bluebell

    Bluebell More % Neanderthal than Adreno but less hairy :-D

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    This is interesting.

    Valentijn, I have some questions for you about this, if you would have time to answer, sometime - obviously there's no rush. :)

    I checked 23andme and I seem not to have GSTT1 either, if I am interpreting it correctly. Along the top, it says, "Your data includes 14 SNPs on gene GSTT1, which is on chromosome 22" but then next to each of the 14 SNPs that are listed, it says for my result "no call".

    Q1 for Valentijn: Does that mean my GSTT1 is completely absent, or that it's present and has some values but their machine just couldn't read any of my SNPs?

    ===
    Seems to be potentially bad:
    "Possible associations with various cancers have been investigated with mixed results....
    The GSTT1 null variant is a risk factor for coronary artery disease in Type 2 diabetic patients, especially among smokers [38].
    Other epidemiological studies have suggested a role in inflammatory airway diseases such as asthma and emphesema [27, 28].
    In a study of samples from White subjects from the Coriell collection, GSTT1 null was found to be in linkage disequilibrium with a deletion of GSTT2B [39]. Cells with the GSTT2B deletion also had lower expression of GSTT2 and a reduced capacity for glutathione conjugation [39]. This linkage may account for some of the discord between studies of cancer risk." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395771/

    After reading the above, I was curious about my GSTT2B status ----- and I may not have it either. 23andme says, "Your data includes 0 SNPs on gene GSTT2B, which is on chromosome 22".

    Q2 for Valentijn: Why does that result look different than my result for GSTT1, which said that my data included 14 SNPs but there was "no call" on all of them? Does only one of these two genes seem to be entirely absent from my genome, or do both seem absent?

    ====
    Q3 for Valentijn, about the below quote from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395771/:

    "Human GSTT1 is constitutively expressed in the liver and can be induced by the consumption of cruciferous vegetables [1, 11].
    GSTT1 is also expressed in the gastrointestinal tract [12], erythroid cells [13], kidney [14] and lung [15].
    Most studies of inducers of GSTT1 has been performed in animal models where NSAIDs, phenobarbital, alpha-angelicalactone, alpha-tocopherol, coumarin and oltipraz induced expression of GSTT1 in the liver or gastrointestinal tract of rodents [1, 16-18]."

    Q: Does that mean, for people who don't have the GSTT1 gene, that eating cruciferous vegetables (like broccoli) or taking Vitamin E (alpha-tocopherol) would not help them to fight cancer, because they have no gene GSTT1 for those ingested substances to induce the expression of?
    Or do anti-cancer substances like vitamins and green tea and certain veggies help to detoxify in other ways that do not require GSTT1 and GSTT2B?
    (I do not know much about biology and such, so forgive me if that's a naïve or nonsensical question.)

    ===
    "Certain alleles, particularly those that confer impaired catalytic activity (e.g. GSTM1*0, GSTT1*0), may be associated with increased sensitivity to toxic compounds."
    http://www.karger.com/Article/FullText/28396

    from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3540796/?report=classic
    "Significant reduction in enzymatic activities and higher risk for malignancies are observed in homozygous “null” genotypes (deletion of GSTT1 or GSTM1 genes), because the detoxifying abilities of these individuals are low."

    Does the body detoxify mainly by the action of just a few genes, so that not having one of them is a pretty big deal?

    ---
    If anyone is interested, here is more information about not having the GSTT1 gene -

    Frequency varies a lot --
    From http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395771/: "...the complete or partial deletion of the GSTT1 gene....varies widely in different populations: approximately 50-60% in Asians, 15% in White populations, 15-20% in Blacks or African Americans, and less than 10% in Hispanic populations."
    from http://www.nature.com/gim/journal/v4/n4/full/gim200238a.html: "The frequency of the GSTT1 null genotype ranges from 15% to 26% in African populations, 16% to 64% in Asian populations, and 10% to 21% in European populations.8 In U.S. populations, the frequency of the GSTT1 null genotype ranges from 22% to 29% in African-Americans, 15% to 27% in whites, and 10% to 12% in Mexican-Americans."

    From http://www.ncbi.nlm.nih.gov/pubmed/12172391/
    "Glutathione S-transferases (GSTs) catalyze the conjugation of glutathione to numerous potentially genotoxic compounds....Individuals with homozygous deletions of GSTM or GSTT have reduced or no glutathione S-transferase activity and therefore may be unable to eliminate electrophilic carcinogens as efficiently."

    from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395771/:
    "The GSTT1 null variant is associated with an increased risk of allergic skin reactions to a variety of drugs, including NSAIDs and antibiotics."
    "A study of large B-cell lymphoma patients treated with rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone showed increased toxicity in individuals with the GSTT1 null variant [52].
    The GSTT1 null variant is associated with increased likelihood of adverse events, including cognitive impairment in pediatric medulloblastoma patients treated with cisplatin, cyclophosphamide, and vincristine [53].
    The null genotype of GSTT1 is also associated with rate of early death after the initiation of chemotherapy in Japanese AML patients treated with cytarabine, mercaptopurine, prednisone and daunorubicin "
    "While the lack of GSTT1 may increase the efficacy of some cytotoxic drugs towards cancer cells due to a reduction in their elimination from the cell, it could also be hypothesized that GSTT1 null individuals might have a poorer prognosis."
  13. Valentijn

    Valentijn Activity Level: 3

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    Sometimes it will have trouble reading individual results, but it can also mean (according to some documentation that they have?) that the gene or part of it is missing. I've looked at a bunch of my genes, and this is the first one where I'm missing more than a few. Basically the whole thing is gone, but the adjacent SNPs from other genes show up as normal. And since a null GSTT1 is a known problem with a fairly common prevalence, it seems extremely likely that most of it missing indicates a null GSTT1.
    GSTT2B is a very small pseudogene. 23andMe doesn't test any of the SNPs on it.

    Yeah, encouraging the expression of a gene that doesn't exist won't do anything for the expression of that gene. It's gone, and we can't bring it back :(

    I have no idea if there's other mechanisms by which those nasty tasting things can be helpful. I would hazard that vitamins and antioxidants will be helpful in general, however.
    There are 15 GSTx genes that I've been able to find, all of which are responsible for hooking up with glutathione with various different toxins. I think there's another 5 also involved in glutathione, and then you also have detoxing genes such as the CYPx family. So GSTT1 is not a huge deal by itself, but it could be a big deal if specifically exposed to the substances which GSTT1 detoxifies, if no other genes are detoxifying it as well.
  14. Beyond

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

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    My urine Taurine was also extremely low. And I am that double CBS C69T mutant. I should be dumping loads of Taurine. So yeah, sometimes SNP´s are not expressed.
  15. Valentijn

    Valentijn Activity Level: 3

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    It's not a matter of expression. There's 0 research indicating that CBS C699T can ever have cause any problematic upregulation of the gene. All of the available research says the opposite, and that it's the -/- which has a slightly greater risk of disease.
  16. Beyond

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

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    I am not sure if that is true or not BUT I would like that Valentijn. And why? Because I can juice my red cabbage! http://nutritiondata.self.com/facts/vegetables-and-vegetable-products/2373/2 And my brocoli! Too healthful to exclude them of my life. :lol: I stopped them for a while when I discovered that supposedly I am sulphur intolerant and now that I take them again it feels good!
    helen1 and Valentijn like this.

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