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Interesting MTHFR Variations

Discussion in 'Genetic Testing and SNPs' started by Valentijn, Aug 2, 2013.

  1. Valentijn

    Valentijn Activity Level: 3

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    Here's MTHFR, in all it's glory. There are lots of missense mutations, which are underlined, bolded, and orange. I added very rare missense mutations to the list even if they don't have research, hence those have a "?" after the risk allele, since it's really just the rare allele and not associated with any risk thus far.

    I left out one of the Yasko SNPs, MTHFR 03 P39P, since the research only shows a non-significant impact. There were also a few SNPs associated with blood pressure only, but because it isn't clear how they effect the gene function (up or down regulation), or even what the risk is (is the higher or lower BP "normal"?), I've left those off the list for now.

    rsID.........NAME....RISK...ETC
    rs2184226....A3301G..C
    rs3737967....R492H...G....T is protective
    rs868014.....R728R...A?...very rare
    rs4846049....A372C...T
    rs35737219...T653M...A?...very rare
    rs2274976....R594Q...T
    rs45590836...M581I...TT
    rs2274974....G566E...T?...very rare
    rs1476413....G35A....T
    rs4846051....F435F...G
    rs1801131....A1298C..G
    rs3927589....E423D...A?...very rare
    rs12121543...G76T....AA
    rs121434296..R377T...A....i5003528
    rs267606886..W339G...CC...i5003529
    rs267606887..N324S...CC...i5003530
    rs121434297..L323P...G....i5003527
    rs1801133....C677T...A
    rs45550133...R134C...A?...very rare
    rs2066472....R68Q....T?...very rare
     
  2. Valentijn

    Valentijn Activity Level: 3

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    So what is MTHFR and why is it important?

    MTHFR stands for methylenetetrahydrofolate reductase, and is the name of an enzyme and the gene which creates it. It creates the active form of folate (5-MTHF), which is necessary for lots of essential things. Being deficient can cause birth defects, elevated homocysteine, anemia, etc.

    Problems with MTHFR being downregulated can be treated by supplementing folate.
     
  3. Bluebell

    Bluebell Senior Member

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    "rs3737967....R492H...G....T is protective"

    For this one, GG is very common - 90% of Europeans, 82% of Asians

    TT is in like .001 of people or something.
    Is even one T protective? That's not very common either - 7% European and African, 16-18% Asian.
    Not many population groups are listed for this SNP in dbSNP, why would that be?

    Why is G risky?

    ----
    I have a couple of the ones you said were "risky", but they are all shared with about 50% of the population. (I have none of the ones that you said were really rare.)

    Is the best way to find out why they are risky to look at Google Scholar (SNP)?

    ----
    When you just have one thingie (that's a technical term) listed in the "Risk" column, like an "A", does it mean that it's risky to be either homozygous or heterozygous, as long as one A is in the pair?

    ----
    When you said (on another thread) that you have presented these SNPs (in your series of reports here) in the order they would be listed when one is reading one's results, what results list are you talking about? The 23andMe data? I typed in MTHFR in the gene search box in my 23andMe data, but my results didn't look like your list in the first post.
     
  4. Valentijn

    Valentijn Activity Level: 3

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    Yes, even one T is protective. No idea why there's not much group data ... some SNPs don't have any at all.
    Because the research shows it is :p Basically the minor allele (T) results in statistically significantly lower homocysteine according to Table at of http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745176/ . By listing "MAF" it indicates that they're talking about the minor allele in the other data, which shows a negative "Beta" value indicating that the minor allele is causing lower levels rather than higher. It also shows a highly significant p-value for the result - basically 0.00000000000041 versus the 0.05 usually used as an upper limit to determine significance.
    Risk and prevalence are not necessarily related, hence a rare version can be more beneficial than the common version.
    Yup, though in the case of some missense mutations, etc, the position for the mutation (such as MTHFR 492) might bring up results in addition to what would be found by searching for "rs3737967". Searching from the NIH site can also bring up additional results (such as by hovering over the cyan result in the gene map on http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs3737967).
    Yes, it means that a study has shown the risk to be associated with the allele or both heterozygous and homozygous genotypes, rather than just the homozygous genotype. Though thus far being homozygous for the risk allele has always indicated a bigger impact - at least, when studies are big enough and the risk allele is common enough for a statistical impact.
    Yes, it should be in order in the 23andMe results. I thought I did one or two of the early ones backwards, but I checked MTHFR and it's in the correct order. It does skip over some of the 23andMe results, since they don't have any impact, and some are only referred to by their "i" numbers (provided in the "Etc" column above).
     

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