The Great VDR Taq/Bsm Debate

[Bluebell]

Do you have a copy of a recent Yasko report or could point me to one?

I don't, myself. You could do a general internet search, and/or start a new thread here to ask forum members to tell you about the VDR area of their Yasko report. My impression is that many PhoenixRising members have had the Yasko analysis done.

 

[Critterina]

I don't, myself. You could do a general internet search, and/or start a new thread here to ask forum members to tell you about the VDR area of their Yasko report. My impression is that many PhoenixRising members have had the Yasko analysis done.

Bluebell,
I created the thread. The CDC website on genetic variants in the populations lists the VDR Taq nucleotide change, (consistent with SNPedia Yasko Methylation if I read it right) as:

rs731236 Ex11+32T>C

So, my GG would be just the opposite strand, matching CC, so to me it looks like I'm the mutant.
We'll see what my new thread turns up!

 

[Bluebell]

The CDC website on genetic variants in the populations lists the VDR Taq nucleotide change, (consistent with SNPedia Yasko Methylation if I read it right) as: rs731236 Ex11+32T>C So, my GG would be just the opposite strand, matching CC

Does the CDC notation indicate which is the result of the majority? I'm assuming that this is what ">" means there.

If that is the case, the fact that T (A) is the majority result and C (G) is the minority result of VDR Taq has not been in question during this discussion --- which has been carried over from a different thread, so you've only seen the tail end of what Valentijn and I were talking about!

Here is one of the posts in the middle of that conversation on that earlier thread: http://forums.phoenixrising.me/index.php?threads/acat-cbs-mtfr-recommendations.24326/#post-373946.

For VDR Taq, Yasko seems to say that the majority result is the riskier result, and the minority result is the safer one.

Saying that the majority's result is the riskier one does not seem to be commonly done (although certainly it's reasonable in some cases to say that it could be the riskier one), and there has been some discussion as to why Yasko would say that about VDR.

I have pointed out in the past to Valentijn that I couldn't really see how my majority result of AA on VDR Taq is especially risky to me, even when reading Yasko's own materials about this SNP.

Valentijn started this thread to say that maybe I was right that Yasko's idea of what is risky and not risky with the VDR Taq and Bsm is hard to square with the research results about them (which might be mixed, but certainly aren't fully negative about the majority's alleles).

The thing is, if SNPedia says that Yasko says that the minority result of VDR Taq is the riskier allele, that does not seem to jibe with any other source of information that I have seen about Yasko's views on this SNP.

...Including GeneticGenie, who has studied Yasko's analyses very closely in order to design his analyses -- he showed in his blog post that Yasko reports it with the majority's alleles being the "risky" ones, and said that he had changed his way of reporting it in January in order to fall in line with Yasko's way. His explanation: http://geneticgenie.org/blog/.

it looks like I'm the mutant.

this was in doubt?

 

[Critterina]

Does the CDC notation indicate which is the result of the majority? I'm assuming that this is what ">" means there.

...

The thing is, if SNPedia says that Yasko says that the minority result of VDR Taq is the riskier allele, that does not seem to jibe with any other source of information that I have seen about Yasko's views on this SNP.

Bluebell,

I read the post you provided the link for. Thanks. I am trying to figure out the notation myself, just having got my 23andMe results less than a week ago. Your comment "Whichever way it is conventionally noted matters to me not one jot, but I think that experts and doctors should use the same genetics notations as each other, out of clarity and simplicity." brought an "Amen! Preach it, Sista!" out of me!

So, to be fair, I had compared the SNPedia Yasko Methylation risk alleles with the left and right sides of the ">" in the CDC chart. They all matched, right side = risky, so I thought I'd cracked that nut. But if this is the ONE instance where the more common variant is the riskier one, well, we'll just have to see what replies my other post elicits. That will tell us if the SNPedia YM matches the Yasko reports. That's probably as much as I'm up for solving right now.

 

[Bluebell]

But if this is the ONE instance where the more common variant is the riskier one.

I asked this of Valentijn the other day on a thread, and she pointed out that Yasko also says the majority allele for
MAO A R297R rs6323 G minority, T majority
is the risky one. I've got TT but Yasko calls that +/+.

That will tell us if the SNPedia YM matches the Yasko reports.

As I've said, I expect that SNPedia is incorrect about this, based on what I've read.

Yasko's VDR views have been a topic of discussion on the forum in the more distant past, I think. Unfortunately, the search function here isn't great because anything less than 4 letters is considered irrelevant, so you can't search for things like taq or vdr, or even vitamin c, for heaven's sake.

 

[roxie60]

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.

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?)

I am also Bsm CC and Taq AA (I have interpreted AA as bad and CC as good), i really have no idea how to interpret, been looking at too many SNPs today. We are fearfully and wonderfully made so I am scared

 

[roxie60]

Bluebell - your quote below was my interpretation also but I still see Taq AA as +/+, the riskier version. My head hurts after reading this thread so not sure what I belive is the risk version of Taq or Bsm (I also do not have Fok, is the an 'i' reference for this one in 23andME, anyone know?)

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 "+/+".

 

[Bluebell]

roxie60
Valentijn later said that Bsm CC and Taq AA are both the majority alleles and that they do usually occur together in the genes (she was mistaken when she said they did not occur together).

Yasko says that Taq AA is +/+ and bad, but I think it's actually fine to have that result and it doesn't do me much harm. Valentijn now agrees with me about this.

Yasko says that Bsm CC is -/-, and that seems to fit with the research.

So I figure my VDR is -/- for both of these SNPs, and I do not worry about it myself.

===
Is that your little kitten, in your image photo? It's so cute!

For me to say that about any kittycat is unusual, because I'm terribly allergic to cats and I usually see them as walking instruments of torture!

 

[Critterina]

Yasko says that Taq AA is +/+ and bad, but I think it's actually fine to have that result and it doesn't do me much harm. Valentijn now agrees with me about this.

Yasko says that Bsm CC is -/-, and that seems to fit with the research.

So I figure my VDR is -/- for both of these SNPs, and I do not worry about it myself.

Bluebell,
My post for Yasko results on VDR Taq didn't really get me any, so I'm back here.

I have to write this down to keep it straight: I am Bsm TT and Taq GG. Genetic Genie marks Bsm +/+ red and Taq -/- green. Per Yasko, then my Bsm TT would be +/+ and my Taq GG is -/-, so Yasko and Genetic Genie do agree. And I followed your link to Genetic Genie's blog. We're cool there, AND I understand now what Valentijn means by homologous. Whew!

On the other hand, SNPedia Yasko Methylation definitely states that for Taq, G is the risk allele. I went to edit the page, but I guess I have to create an account or it records my IP address when I make an edit...have to be another day.

 

[Sea]

In general the > symbol is used to denote a changed allele (or protein). Take for example MTHFR 1298: It can be written as A1298C or 1298A>C. It doesn't have anything to do with the frequency or risk.

Sometimes a change has been made so far back in history that almost everyone now has the changed allele. I don't really know how they determine which one is ancestral and which one is the change but that doesn't really matter to our discussion.

It is often the case that the changed allele is dysfunctional, but sometimes there is no change to function and sometimes there is even a positive benefit to the change. Sometimes it can be protective for one illness and yet raise the risk of something else. So being the major or minor allele doesn't help with determining risk, other than saying something that the majority of people carry can't be too bad.

Usually the + symbol (either +- for one allele or ++ for 2) means positive for a change. It becomes confusing because some people only use it to mean risk regardless of change, some only use it to mean change with or without risk.

Adding to that confusion with the Taq in particular is that Yasko has changed the way she reports the risk for this in the last couple of years and Genetic Genie followed this year. I don't think she changed her mind about the risk allele, just the way she reported it, though I could easily be wrong there.

Since I am heterozygous for Taq and Bsm I haven't invested a lot of time to finding out which allele is the risk

 

[Critterina]

In general the > symbol is used to denote a changed allele (or protein).

Sea,
Thanks for that info. I have also seen the < sign used on the CDC website (MBL2 gene). What does that mean?

 

[Sea]

Sea,
Thanks for that info. I have also seen the < sign used on the CDC website (MBL2 gene). What does that mean?

Sorry, I don't know. I've not seen it written that way before

 

[Valentijn]

Thanks for that info. I have also seen the < sign used on the CDC website (MBL2 gene). What does that mean?

I think that's used sometimes in studies where they're describing the location of the SNP on the gene.

 

[Critterina]

I think that's used sometimes in studies where they're describing the location of the SNP on the gene.

Valentijn,
The example below is from their chart (with my results inserted 4th column). The < is in the 5th column, next to last row. I don't know how to read that column to begin with. Can you explain? Thanks!


MBL2 Mannose-binding lectin (protein C) 2, soluble (opsonic defect) rs11003125 C CG -618G>C Immunity and inflammation Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases. http://www.ncbi.nlm.nih.gov/gene/4153
-550G>C
rs1800450 A CC Ex1-27G>A Gly54Asp
rs1800451 A none Ex1-18G>A Gly57Glu
rs5030737 T GG Ex1-34C>T Arg52Cys
rs7096206 C CG -289G<C
-221G>C

 

[Valentijn]

Valentijn,
The example below is from their chart (with my results inserted 4th column). The < is in the 5th column, next to last row. I don't know how to read that column to begin with. Can you explain? Thanks!

Either it means something I'm not familiar with, or it's a typo. I'm learning toward the typo explanation, since the "G>C" is quite standard, and if it was a matter of C being the reference allele, it'd just be displayed the other way (C>G, not G<C). And typos happen fairly often with rsID's and such - spell check won't catch those or symbols.

That table is just displaying basic data about the SNPs they're looking at - no results are in there. The next table is looking at allele and genotype frequencies for different ethnic groups, and because the "P value" is less than 0.05, the difference between races is significant. The next table looks at age differences (possibly to determine if one genotype or allele is results in earlier death?), but finds no significant difference, because the p-value is quite high.

So basically that study is showing no effect based on which version of rs7096206 someone has. Though there still might be other areas in which it has an impact.

 

[Critterina]

I'm learning toward the typo explanation, ... no results are in there.

So basically that study is showing no effect based on which version of rs7096206 someone has. Though there still might be other areas in which it has an impact.

Thank you! That table didn't paste in at all the way I wanted it! I was wondering if that could be a typo. What I pasted did have my results, as you can see the occasional CC and CG in there...but it's hard to follow without the table format. No matter.
The link was not to the table - sorry.

 

[Moshi]

I've been trying to make sense of this thread but all this info is like a vertical learning curve for me!

I'm homozygous for VDR Bsm rs1544410 TT

I have been supplementing with vit D for the past two years but no extreeme dose, less than 1000 IU daily, HOWEVER, my recent lab test shows that my D25 serum levels are close to TOXIC (240 nmol/L)!!!

And I thought I needed more vit D due to my VDR Bsm +/+ status....!? Needless to say I will not supplement for awhile...however, even though my serum levels are high, that does not necessary mean that my body can use it....or?

Thankful it anyone here could simplify this/clarify this.....anyone?

 

[Valentijn]

And I thought I needed more vit D due to my VDR Bsm +/+ status....!? Needless to say I will not supplement for awhile...however, even though my serum levels are high, that does not necessary mean that my body can use it....or?

VDR Bsm has a relatively small impact on VDR function, so supplementing might not be necessary for you.

And it's also very important to keep in mind that VDR is the receptor for vitamin D, not a producer of vitamin D. Thus if someone does have poorly functioning VDR, vitamin D levels might get somewhat high due to not getting used properly by the body. Yet if VDR is badly dysfunctional, the solution is to take more vitamin D, probably because that ensures that the existing VDR is constantly hooking up with vitamin D, and therefore working as efficiently as it can.

I don't think Vitamin D can be toxic in itself - the toxicity would come from elevated calcium as a side-effect of elevated vitamin D levels. So getting calcium levels tested might give a better indication of whether your levels are problematic. I've also made a list of problematic and rare VDR mutations at http://forums.phoenixrising.me/index.php?threads/interesting-vdr-variations.24480/ , some of which have a much bigger impact than Bsm.

 

[Moshi]

Wow! Valentijn, thank you so much for summarizing this for me. Now I totally get it.
And I am prepared for my next conversation with my doctor, who I think will accuse me of having taken crazy doses of vit D, which I really have not.
Thanks again for taking your time!!

 

[Msinnott]

I am vdr bsm +/+ and found my 1,25 levels were really high compared to my 25oh levels. This was on 10,000iu of vitamin d I have since went down to 5000iui and started supplementing calcium and mk7 my 1,25 levels have dropped 50 points in 2 months.