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mthfd1 g1958a rs2236225 could this be similar to MTHFR 677?

Discussion in 'Genetic Testing and SNPs' started by Kimsie, Oct 29, 2013.

  1. Kimsie

    Kimsie Senior Member

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    "A common mutation at position 1958 within the MTHFD1 gene results in a transition of guanine to adenine (G>A) that may result in a reduction in folate metabolism. In some populations individuals who are homozygote for (1958AA) are reported to have a higher risk for neural tube defects, gastric cancer, schizophrenia and bipolar depression. " http://www.baylorhealth.edu/Researc...ydrogenase(MTHFD1)G1958Amutationanalysis.aspx

    I can't find a lot of info on this one. I am wondering how much it reduces the ability to methylate folate. Anyone know about this?
     
  2. Sea

    Sea Senior Member

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    I haven't followed up any of the links, but here's the snp if you're interested
    http://snpedia.com/index.php/Rs2236225
     
  3. roxie60

    roxie60 Senior Member

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    wonder if it applies to other MTHFD1 SNPs?
     
  4. Kimsie

    Kimsie Senior Member

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    This was the only one that I saw a study on that seemed to indicate that it was a downregulation.
    Thanks, Roxie, I did look at SNPedia. It's hard to find studies that show what the mutation does, upregulation, downregulation or what.
     
  5. Valentijn

    Valentijn Activity Level: 3

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    http://www.ncbi.nlm.nih.gov/pubmed/18767138 discusses what's happening - basically there is a missense mutation, where one amino acid is substituted with another for the "A" allele. The substituted amine acid forms a weaker bond in the enzyme which the gene forms, hence it breaks down a lot faster. When enzymes break down faster, they do a lot less work, and are generally less efficient at doing their jobs.

    Metabolic activity of the protein created by the gene is reduced by about 26%, so AA is a down-regulation. Risk of heart defects is 2-3x higher when homozygous than in the general population.

    According to http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732995/table/T2/ having AA for rs2236225 and rs1076991 TT means a 3.34x higher risk of neural tube defects (associated with low folate status).

    But according to the first study, there are a couple ways to brings various levels back to normal: one is with magnesium adenosine triphosphate and the other is by supplementing folate directly. Even though the problem with the gene does not caused reduced folate levels, it's often the case that having more of the substance which the enzyme needs can make the existing enzymes more efficient, possibly because the few MTHFD enzymes which are present can run into their needed components (derived from folates) more frequently.
     
  6. PDXhausted

    PDXhausted Senior Member

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    @Kimsie

    Thank you for posting this and the FOLH1 thread. I am homozygous for both (rs2236225 AA and rs202676 GG). I was feeling pretty lukewarm about folate being my issue since my MTHFR C677T is normal and I am only heterozygous on A1298C, and my serum folate test was normal when I first got sick. Now seeing the research on these SNPs makes me more motivated to do more research and test out methyl-folate. Thanks @Valentijn for researching this as well.

    Now if only the potential for potassium deficiency didn't scare me so much!
     
  7. Valentijn

    Valentijn Activity Level: 3

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    I haven't heard of folate supplementation alone causing potassium problems. And if you're taking B12, hydroxoB12 should avoid the potassium problem.
     
  8. Kimsie

    Kimsie Senior Member

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    Thanks, Valentijn, that is a big help. We have a son who has schizophrenia, and although since we had the Yasko panel done on him and not the 23andme, we know that he doesn't have MTHFR 677, so it seems like folate shouldn't be a problem, but now that I had myself and his 3 siblings done with 23andme it turns out that one sibling is ++ for the FOLH1 gene and I am +- for the MTHFD1 so to play it safe I have giving him 5mg of methylfolate even though there isn't anything on his Yasko panel which shows that he needs it.
     
    Valentijn likes this.

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