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Interesting VDR Variations

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

  1. Valentijn

    Valentijn Activity Level: 3

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    Correct. VDR Taq G is the slower allele, hence the one which would use up less methyl groups, and possibly cause less tolerance of supplements containing methyl groups.
     
  2. LynnD

    LynnD

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    Would some of these effect how absorbing vite D or how transporting it or how utilzing it?
    I usually have low, even though eat organic turkey liver, out in sun...
    if take alot, got leg cramps, so probably need with minerals and maybe K (all in liver I think and onions and vegies).
    They just said osteoporosis and biophosphates,dont want those, heard bad things. Cant increase menerals more or get more stomachaches. only have 1 of "risky" rs11574115...T362I...GG, rs731236.....Taq1 GG, rs886441. C4004T AA,will ck others later.
    what do intergenics mean?
     
  3. Valentijn

    Valentijn Activity Level: 3

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    VDR is just triggered by vitamin D. But if there's low vitamin D, it can make VDR problems even worse, and supplementing D3 can help VDR function better if it has a problem.
     
  4. LynnD

    LynnD

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    Thanks
    ok, will go find the D3 bottle, (seems to be ok to put on skin)
    and try some.
     
  5. Critterina

    Critterina Senior Member

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    Thanks for this thread, Valentijn!

    I'll go back and edit my thread from last night to include these, but I seem to have a few :sluggish: (sluggish) ones:

    rs11574115...T362I...G.....GG..... +/+
    rs731236.....Taq1....G.....GG..... +/+
    rs7975232....Apa1....A.....AA..... +/+
    rs1544410....Bsm1....T.....TT..... +/+
    rs2239179....A1064G..T.....TT..... +/+
    rs886441.....C4004T..A.....AA..... +/+
    rs3819545....T6046C..G.....GG..... +/+
    rs11168287...C8857T..GG.....GG..... +/+
    rs7139166....G1520C..CC.....CC..... +/+

    I had been a bit concerned that I was advised to keep my serum Vitamin D above 70 (reference range 30-100), or, the way I think of it, above 57% of the reference range. I need to take 10,000 IU of D3 daily to do this, and it seemed kind of high. I think I won't worry about it, from what you say about needing to have the D always present for the VDR to always find it.

    Thanks, too for that last link to the publication - being a woman, I didn't worry about the cancer part, but the list of 4 Vitamin D metabolizers and 8 signalers gives me some other genes to look into that might explain why I need to take so much of it. I'd put my money on a fast-metabolizer variant or two.
     
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  6. Valentijn

    Valentijn Activity Level: 3

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    I've got a correction to make to the initial list (already updated) - there's no known risk associated with T362I. Rather it should have been flagged with "A?" instead of "G", as the A variant is very rare and hence somewhat interesting.

    Something else to keep in mind is that when Bsm1 and Taq1 match up, they're basically saying the same thing, and having both of them is no worse than having one of them.

    I double checked your other results with my notes, and they're correct :p
     
    Critterina likes this.
  7. Critterina

    Critterina Senior Member

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    OK, so I'll take T362I off my list. Genetic Genie had put my Taq rs731236 as -/-, so I was surprised it came up +/+ here.
     
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  8. Valentijn

    Valentijn Activity Level: 3

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    They go with the Yasko interpretation to keep the fans happy :p But almost all of the research says the Bsm +/+ and Taq -/- are the marginally riskier versions. The real problems might occur when Bsm and Taq aren't matching up.
     
  9. Critterina

    Critterina Senior Member

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    Good appointment today, and this discussion of having Vitamin D available when your receptors are slower came into play. I thought I'd be the first to lobby for a lower dose, but instead she suggested it and I defended staying where I was in order to be at the Vitamin D serum level that she wants me at. Practical, practical!;)
     
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  10. Valentijn

    Valentijn Activity Level: 3

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    Just to clarify, the extra vitamin D can result in vitamin D levels getting high. But that can help keep VDR activity at normal levels, when your VDR has slow mutations.
     
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  11. Critterina

    Critterina Senior Member

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    Thanks for the clarification. My Vitamin D levels are now at 64% of the reference range - I wouldn't say that's high, but it's probably good not to reduce my dose.
     
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  12. Gondwanaland

    Gondwanaland Senior Member

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    @Valentijn Please apologise my brain fog, I read all this topic + others about VDR, but could not reach a conclusion about having

    VDR Bsm rs1544410 CC -/-
    VDR Taq rs731236 AA +/+

    My questions are:
    Is Bsm CC in fact the good version?
    Is Taq AA in fact the bad version?
    In any case, they don't match :eek:

    What are the implications?
    Is supplementation recommended?

    Those are DH's versions. Last year his Vit D 25 OH levels have been tested for the first time and were 13 (mine were 12). We supplemented and mine went to 49 while DH's went to 30. He has never had his 1,25 vit D levels checked.
     
  13. Valentijn

    Valentijn Activity Level: 3

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    @Gondwanaland - Neither VDR Bsm or VDR Taq have much impact. Yasko reports them in a contradictory manner - so literally everyone is homozygous for one, or heterozygous for both. Clueless error or profitable marketing technique? :p

    You have the "good" version of both, though I don't think even the slow versions of those would warrant supplementation by themselves. However, supplementation of vitamin D is often still a good idea if you're pretty housebound with any illness and not getting sufficient UVB exposure.
     
  14. Gondwanaland

    Gondwanaland Senior Member

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    Thanks, @Valentijn
    I think finding out the 1,25 vit D levels is the more important instance after all!
     
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  15. Valentijn

    Valentijn Activity Level: 3

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    I've updated the first post to indicate which mutations have definite disease associated with them. Basically all of the missense mutations tested by 23andMe, except one, are known to cause rickets (a result of significant Vitamin D deficiency). Because VDR mutations result in reduced binding with Vitamin D, Vitamin D levels could be normal or high in people with these mutations.

    Some mutations create "Vitamin D Dependent" rickets, which means that large doses of Vitamin D can compensate for reduced function, probably due to the reduced number of functional VDR receptors having a greater chance of encountering Vitamin D when it is supplemented. But Vitamin D Resistant rickets isn't helped by Vitamin D, because it's the part of the encoded protein which has to combine with the Vitamin D which isn't functioning.

    VDR Rickets is an autosomal recessive, which means that someone has to be homozygous for one of the missense mutations, or compound heterozygous, to have a disease resulting from it. 23andMe can't indicate if someone is compound heterozygous because they put alleles in alphabetical order instead of showing which ones come from the mother and which ones come from the father. So if compound heterozygosity is possible, it might be good to have a more thorough VDR gene test run.

    The rest are synonymous mutations (not missense mutations) which have a little impact upon disease risk, and none of them have research indicating that they have a direct impact on VDR amount or functionality. Due to the indirect and tenuous nature of the research into those SNPs, I don't have a lot of confidence that they actually have an impact, much less a significant impact.
     
    merylg likes this.

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