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The Great VDR Taq/Bsm Debate

Discussion in 'Genetic Testing and SNPs' started by Valentijn, Jul 29, 2013.

  1. Valentijn

    Valentijn Activity Level: 3

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    Bluebell
    You might be right about VDR Bsm TT being the risk version. One study explicitly says that the T version is down-regulated. There's also a study showing less cancer risk for that (most studies show slower VDR = increased cancer risk), but the T version is also showing more risk of lupus and ANA.

    Because it shows T is down-regulating the VDR gene, and VDR generates dopamine which uses up methyl groups, the slow T version should result in more methyl groups floating around than the faster C version.

    To complicate things a bit, I've found one study saying T results in shorter height, and another showing that TT results in taller height. But the showing of downregulation and associated risk factors seems to be the most consistent thus far.

    To make life simpler in general when reading the research, Bsm "B" = A/T, and Bsm "b" = G/C.

    I haven't looked at the Taq info in detail again yet. It'll probably completely contradict all the Bsm research, knowing my luck :p
     
  2. Valentijn

    Valentijn Activity Level: 3

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    Something else I'd like to put into this thread is that even though Taq and Bsm are usually synonymous, it might mean trouble when they aren't. As an example of what synonymous means for SNPs : almost everyone with Taq GG will have Bsm CC. It's very rare to see someone with Taq GG and Bsm CT, for example. If someone has a certain allele in Taq, you usually know what their allele for Bsm will be.

    Looking at the last table in http://www.researchgate.net/publica..._rickets_carriers/file/79e41500e3712b4614.pdf there seems to be far higher prevalence of non-synonymous Taq/Bsm results in carriers than controls. Is there any other research out there which more directly investigates the issue?

    It's possible that the non-synonymous Taq/Bsm is a much bigger risk factor than having the synonymous "bad" version of Taq/Bsm. Though I'm not sure how that would work.
     
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  3. Bluebell

    Bluebell Senior Member

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    Complicated! :ill:
     
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  4. Valentijn

    Valentijn Activity Level: 3

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    VDR Taq AA augments (increases) VDR gene expression according to a study, and protects against MS according to another study. This would seem to mesh with the view that Bsm TT/Taq GG is the riskier/slower version.

    I think the biggest area of confusion is around Vitamin D 25 levels. Low vitamin D generally is bad, but if it's higher because there's not enough VDR to take it up as easily and do something useful with it, then higher is bad.
     
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  5. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    So, would BSM TT sometimes be noted as BSM bb (as opposed to BB)?

    Sushi
     
  6. Valentijn

    Valentijn Activity Level: 3

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    I sure as hell hope not, because that would send me around the bend :p

    From what I've seen, it should be pretty consistent throughout the studies that use BB/bb instead of TT/CC. The lower case is the "wild type" and upper case is for the variant.
     
  7. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    The possible confusions are endless--and I think I just got confused! Mine came back as BB with the notation: moderate to low responder (to GcMAF, that is), so that would be the risk type. :( I also had ff for FOK which I think is also the risk type.

    Sushi
     
  8. Critterina

    Critterina Senior Member

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    So if Taq GG and Bsm CC are synonymous, and Taq GG and Bsm CT is rare, what is Taq GG and Bsm TT - more rare? (I always knew I was special.)

    My first post - see if it works!
     
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  9. Bluebell

    Bluebell Senior Member

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    Critterina, it worked! Welcome to the forum. :)

    =======
    Valentijn, I have Taq AA and Bsm CC. Is there something weird about that combination? Do most people with Bsm CC have Taq GG?

    I can't see the rickets paper you linked to (I'm not a member there and I can't handle signing up for anything tonight - lots of brain fog.) However, my Vitamin D is totally deficient, so I wonder if I'm one of the 'mutant' (term used affectionately!) non-synonymous VDR people in that table you mentioned.

    You wrote: "It's possible that the non-synonymous Taq/Bsm is a much bigger risk factor than having the synonymous "bad" version of Taq/Bsm." Hmm.

    But -- I've just had a look in my chart of genetic results, and it says that Bsm CC is the major allele, and Taq AA is the major allele (therefore, for both of them, my result is the result of most people). I wonder how they both can be the result of the majority of people, yet not usually combined together in the same individual? (Did I read dbSNP wrong for those two?)
     
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  10. Critterina

    Critterina Senior Member

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    Thanks, Bluebell! I see we are VDR-opposite mutants (still used affectionately). I thought mine were the homozyous risk alleles - did I get that wrong? After 10 months on 6000 IU of D3, I tested in the mid 60's - much progress, I think, but then I started a protocol and it dropped, so they upped me to 10,000 IU for 3 months. Waiting test results.
     
  11. Bluebell

    Bluebell Senior Member

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    Hey Fellow Mu :alien: ,

    As far as I understand it (so, not very far....)

    Your two VDR alleles are those of the minority of people, and mine are those of the majority of people. Many times, the alleles that the majority has are seen as the less risky alleles to have. But not always.

    In Dr. Amy Yasko's reckoning, one of your alleles is LESS risky than one of mine, and that is the VDR Taq. She says that the majority's result on VDR Taq, AA, should be called "+/+" = risky. She calls your result, GG, "-/-" = less risky.

    Well, that's what she used to do. Now, I guess that she's changed her designation and she's using upper and lower case letters. I really don't understand what it all means.

    See: http://forums.phoenixrising.me/index.php?threads/dr-vank-the-vdr-changes.18858/ Quote from Yasko: "As with everything else related to VDR, there is disagreement whether the shorter stretch of A’s (Bt) or the longer stretch of A’s (bT) grants more stability to the protein. Reports regarding which genotype is associated with a range of diseases or health conditions vary depending on the researcher. To try to keep things clear, in the future we will use the tt or TT designation to denote VDR Taq and FF and ff for Fok. Those who are tt should consider limited methyl donors. Those who are TT tend to have a greater tolerance for ie methylB12. Again, the bottom line is that I do feel low dose vitamin D plus rosemary and sage and resveratrol are a positive for all. This is especially true as there is conflicting literature regarding disease susceptibility and the various VDR SNPS that at times is totally contradictory."

    I don't even know about Fok. I do not have Fok in my homemade chart.

    And I do not know what Yasko does with VDR Bsm, because I didn't get her report for myself. When I looked Bsm up on 23andMe (rs1544410), and then on dbSNP, I noted down in my spreadsheet that it was AA (TT) for the majority and GG (CC) for the minority, so because I had CC (GG), I put down in my chart that mine were the majority result for that one. And I gave myself a "-/-" on that one in my chart, because I chose it to be less mutated than the minority's result, based on probably no research. :D
     
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  12. Critterina

    Critterina Senior Member

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    Bluebell,
    I did the same regarding looking up by rs number, but I got the version of which one was the risk allele from the SNPedia Yasko Methylation page. http://snpedia.com/index.php/Yasko_Methylation. I did the same with the CDC Genetic Variants http://www.cdc.gov/genomics/population/genvar/genetic_variants_t1.htm. I listed the risk allele as the letter after the > in names like Ex4+13G>C. So, SNPedia thinks that Yasko thinks that the risk allele for Bsm is T and for Taq is G and for Fok is T (reported as A in 23and Me). But like you, I didn't get anything for Fok rs10735810 in my 23andMe file.
    I read the article on VDR changes. It looks like a pretty young science, when people can invent their own nomenclature and expect others to fall in line. To me, it's just confusing. But who knows, maybe tt and FF will prevail.
    I hadn't heard of rosemary and sage and resveratrol to be used with Vitamin D. And my D dose isn't low. I wasn't happy that we went 3 months on 10,000 IU before testing yesterday.
    What's confusing to me is that we sometimes associate more stability in the protein with it coming from a lower risk variant, when I'm not sure that's always the right conclusion. Maybe some rate of protein breakdown is optimal. I read another comment about the people with the riskier (of some) variant lived longer than the people without it, so it should be the less risky allele. It never dawned on him that longevity and health are not synonymous.
    Bluebell, it's nice to make your acquaintance. Thank you.
     
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  13. Bluebell

    Bluebell Senior Member

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    Ooh, my head hurts!

    I thought that Yasko thought that the risk allele for Taq is A -- she calls AA "+/+", I thought. And she calls GG "-/-".

    Therefore, if SNPedia says that Yasko says the risky one for Taq is G, I think SNPedia could be wrong on that, because see below what GeneticGenie said about changing his Taq designation to fall in line with Yasko's:
    It shows up in the following chart that she is calling a VDR Taq of C (G) to be a "-/-" even though that's the minority result : http://geneticgenie.org/blog/. GeneticGenie says in that blog post that he was reporting it the conventional way of "+/+" until January, when he decided to go with the Yasko way and call it a "-/-".

    So either GeneticGenie or SNPedia is correct about Yasko's view of Taq....

    I guess the only way to know for sure is to find someone who got a Yasko report done and see what Yasko called it in the report.

    Although, I triangulated quite a few people's Yasko reports (which they had published online, here at PhoenixRising and elsewhere on the internet) when I was making my homemade chart, and I am pretty sure that what I put in my chart was what they all had agreed on, which is that Yasko called a Taq of AA to be a "+/+".


    Uh-hunh, it's like Simon and Garfunkel sang in the 60s, "Are you going to (increase your Vitamin D at) Scarborough Fair? Partly sage, rosemary and wine*!" :p

    *red wine=resveratrol
     
  14. Valentijn

    Valentijn Activity Level: 3

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    Whoops, sorry ... I was probably looking at the Yasko list and forgot to invert one of the results (since she has them reported backwards).
    Bluebell too:
    Taq GG and Bsm TT (or Taq AA and Bsm CC) would be the normal synonymous versions. Taq GG and Bsm CC, or Taq AA and Bsm TT, would be the non-synonymous versions.

    In the study I looked at which had homo-hetero nonsynonymous, the homo-homo non-synonymous varieties weren't present at all, so probably are even rarer.
     
  15. Valentijn

    Valentijn Activity Level: 3

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    I think it's available if you just click the full text icon on the right near the bottom, and then you have a download option too, but here's the relevant table:
    Table 3. Different combinations of VDR polymorphisms in HVDRR heterozygotes and controls
    .........Controls Carriers
    FFBBAATt 0........2
    FFBBAAtt 8........4
    FFBbAATt 3........0
    FFBbAaTT 1........0
    FFBbAaTt 12.......2
    FFBbaatt 0........1
    FFbbAaTT 3........0
    FFbbaaTT 3........0
    FfBBAAtt 2........2
    FfBBAatt 1........0
    FfBbAATT 0........1
    FfBbAATt 1........3
    FfBbAaTt 3........2
    FfBbAatt 0........3
    FfbbaaTT 3........0
    ffBbAaTt 1........0
    Total....41.......20

    Supposedly bb (Bsm TT) and TT (Taq GG) should be the riskier versions based on various research finding small but significant effects. Yet it's the controls which have those haplotypes, while 7 out of 8 non-synonymous results are in the rickets carriers. So 7 out of 20 carriers are non-synonymous, and only 1 out of 41 controls are non-synonymous.
     
  16. Bluebell

    Bluebell Senior Member

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    my head just exploded, thank you

    I tried it the other day when I first saw your mention of it, and again earlier tonight - I get a big window across the screen that tells me I need to be a member to see anything at all.

    Critter and I are not VDR mutants after all! And with that, I shall collect the larger pieces of my head and tumble into bed for the night.
     
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  17. Critterina

    Critterina Senior Member

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    Bluebell,

    how do you do multiple quotes in a reply?

    No red wine for me! I'd look like that little pink face with the tongue out, minus the smile! I have no gene for the flush reaction, but I do get all red. I'm CBS +/-, so I figured it might be a SUOX thing. I just checked my sulfite/sulfate for the first time. Sulfite was low (10-25 range) and sulfate was in the 800-1200 range. Not bad for 3 months of 1500 mg Me, 1800 mg of NAC, and 200 mg of ALA that I just stopped this weekend, I suppose.

    I'll look into the Taq thing, and if SNPedia is wrong, I can edit it. We'll chat first.
     
  18. Bluebell

    Bluebell Senior Member

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    You can copy and paste the instructions for making something look like a quote, and place them around the part of the reply you want to quote, and delete the rest of that person's reply that you don't want to quote.

    By which I mean, copy and paste the thing that looks like the following but with brackets [ ] around it, which goes before the quoted section:
    quote="Critterina, post: 374936, member: 11590"

    and the thing that looks like the following but with brackets around it [ ], which goes after the quoted section:
    /quote

    I had to leave the brackets out above to show you how it looks, but you need to copy and paste the brackets also, to get it to work.

    And put those 2 sections before and after the part of the person's comment that you want to show up as a quote in your comment.

    No probs, I'll have your portion. ...Yoo-hoo, Waiter! :D

    How do you test for those? Blood test?

    What condition was this protocol meant to treat? Did it help?

    That would be good. I think that someone else mentioned the other day that SNPedia had confused her about her VDR results.
     
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  19. Critterina

    Critterina Senior Member

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    I was just looking to see if you're near Tucson, as I have a few bottles to donate. No could see.
    I bought test strips off Amazon. Scientific Instruments of Houston, I think, was the only supplier. It's about $70 with S&H. I thought the sulfite strips were a waste, if I'm low already (but good to know probably no SUOX), until I put some coconut syrup in my tea this morning. I ruined it. I thought "I bet this has sulfites in it". So I got out the test strip, diluted the coconut by about 24x (1/4 tsp in 2 T water) and it came back at 50 mg/L. Arrgh! The rest (tea ans syrup) went down the drain. And I didn't feel so stupid for buying the test strips. From what I read on here, everybody's test strips have the same markings, so the manufacturer is not important. Except Yasko's have to be refrigerated.
    The ALA was part of the supplements for muscle wasting from back in January. (Test result was 3-methyl histadine). Then when I retested in April, my tryptophan was half low normal and my methionine was just below normal. There was no real understanding of the other possible mutations on the part of my RN. I had wondered about negative reactions to sulfur to her, but no response.
    Well, then the next time SNPedia pops a little box up and asks me if I've made an edit, I'll say yes. When I checked the 'no' box, I was wishing they had a "No, are you kidding? I've never been here before!" box
     
  20. Critterina

    Critterina Senior Member

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    Do you have a copy of a recent Yasko report or could point me to one? I'm the type that needs to verify before making an edit.
     

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