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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
     
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  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.
     
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  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.
     
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  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.
     
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  16. picante

    picante Senior Member

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    Helena, MT USA
    @Valentijn, I finally compared your list with my VDR gene results. Most of your list was not tested by 23andme, but these were:

    VDR 48238068 rs3847987 A or C (T) CC
    VDR 48238728 rs11574115 A or G (A) (?) GG
    VDR Taq1 48238757 rs731236 A or G (G) GG
    VDR Tru91 48239675 rs757343 C or T (C) CC
    VDR Bsm1 48239835 rs1544410 C or T (T) TT
    VDR A3419G 48255411 rs2239182 C or T (CC) CT
    VDR G166A 48259126 rs12717991 C or T (C) CT
    VDR C4004T 48262964 rs886441 A or G (A) AA
    VDR T6046C 48265006 rs3819545 A or G (G) AG
    VDR C6584G 48266167 rs3782905 C or G (C) CG
    VDR T3341C 48269410 rs2239186 A or G (G) AA
    VDR G4817A 48277713 rs2238136 C or T (T) CC
    VDR C8857T 48285414 rs11168287 A or G (GG) AG

    I put the risk allele in the second-to-last column. [Edit: ack! my spacing all disappeared. So I just put parentheses around them.]
    Mine look OK, except for Taq1, Bsm1, and C4004T, which are all +/+.
    Would you agree?
     
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  17. Valentijn

    Valentijn Activity Level: 3

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    Yes, those are all pretty mild ones. And Bsm1 and Taq1 are basically echoing a single alteration in gene function, so aren't both having an additive effect. So it's looking like two pretty minor down-regulations.
     
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  18. xptriado

    xptriado Senior Member

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    I am a bit confused.

    Having a vdr problem as in having the above mentioned mutations, would lead to a dysfunctional.receptor or to less receptors?
     
  19. Valentijn

    Valentijn Activity Level: 3

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    It would probably depend on where the mutation is. Mutations which have an impact usually do so by causing the protein to break down a bit faster, so there will be fewer receptors. But VDR mutations which impact the ability of the protein to interact with other proteins might not break down any faster but could prevent Vitamin D from hooking up with the VDR.

    And non-coding mutations could potentially decrease the amount of VDR produced in the first place. Though these usually don't seem to have a big impact, compared to the coding mutations.
     
  20. bertiedog

    bertiedog Senior Member

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    @Valentijn

    Here are my results, would you mind having a look?


    Gene Position SNP Versions Pam Genotype
    VDR 48235702 rs11574138 C or T TT
    VDR 48235936 rs11168263 C or T TT

    VDR 48236303 rs11574136 A or G GG
    VDR 48236392 rs12721386 C or T no call
    VDR 48236664 rs11540149 C or T CC
    VDR 48236863 rs11574134 G or T TT
    VDR 48237158 rs1042945 C or T CC
    VDR 48237210 rs11574131 A or G GG
    VDR 48237248 rs7967673 C or T CC
    VDR 48237303 rs11574129 A or G AA
    VDR 48237735 rs11574126 C or T CC
    VDR 48237781 rs11574124 A or C AA
    VDR 48237840 rs11574123 A or G GG
    VDR 48237881 rs11574122 G or T TT
    VDR 48237928 rs11574121 A or G GG
    VDR 48237967 rs3858733 G or T TT
    VDR 48238068 rs3847987 A or C CC
    VDR 48238175 rs11608995 C or T TT
    VDR 48238221 rs739837 G or T GT
    VDR 48238345 rs11574116 A or C AA
    VDR 48238642 i5000776 A or G GG
    VDR 48238715 rs34189316 A or G GG
    VDR 48238728 rs11574115 A or G GG
    VDR 48238757 rs731236 A or G AG
    VDR 48238777 i5000773 C or T CC
    VDR 48238837 rs7975232 A or C AC
    VDR 48239675 rs757343 C or T CC
    VDR 48239835 rs1544410 C or T CT
    VDR 48240157 i5000774 C or T CC
    VDR 48240201 i5000777 A or C AA
    VDR 48240248 rs11574107 C or T TT
    VDR 48240526 i5000780 A or C CC
    VDR 48244184 rs7967152 A or C AC
    VDR 48244559 rs2239185 A or G AG
    VDR 48244583 rs2239184 A or G AG
    VDR 48249633 rs7966569 A or G AA
    VDR 48251295 i5000781 A or G GG
    VDR 48251305 rs2229828 A or G GG
    VDR 48251542 rs11168267 A or G no call
    VDR 48253356 rs2248098 A or G AG
    VDR 48255411 rs2239182 C or T CC
    VDR 48255570 rs2107301 A or G GG
    VDR 48255859 rs2283342 A or G AA
    VDR 48255949 rs2239181 A or C AA
    VDR 48257326 rs1540339 C or T CC
    VDR 48258877 i5000783 C or T TT
    VDR 48258958 i5000782 C or T CC
    VDR 48259126 rs12717991 C or T CC
    VDR 48262964 rs886441 A or G AG
    VDR 48263828 rs2189480 G or T GG
    VDR 48265006 rs3819545 A or G AA
    VDR 48266167 rs3782905 C or G CG
    VDR 48269410 rs2239186 A or G AA
    VDR 48272275 rs11168275 C or T CT
    VDR 48272743 rs10783218 A or G GG
    VDR 48272760 i5000779 C or T CC
    VDR 48272809 i5000775 A or G GG
    VDR 48272849 rs11832059 A or G AA
    VDR 48272895 rs2228570 A or G GG
    VDR 48273714 rs2254210 A or G GG
    VDR 48276432 rs11574040 A or G AA
    VDR 48277713 rs2238136 C or T CC
    VDR 48285414 rs11168287 A or G AA
    VDR 48285648 rs4328262 G or T TT
    VDR 48286015 rs4334089 A or G AG
    VDR 48287203 rs4237855 A or G AA
    VDR 48287373 rs11574027 A or C CC
    VDR 48288246 rs11574026 A or G GG
    VDR 48289373 rs3890733 C or T CT
    VDR 48293716 rs11168293 G or T GT
    VDR 48294131 rs4760655 A or G AA
    VDR 48296268 rs7299460 C or T CT
    VDR 48296486 rs4760658 A or G AG
    Many thanks
    Pam
     

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