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@WE6588 I have the same VDR Bsm as you, ++ and VDR Taq --. I, too, am not sure what it all means. My son has VDR Bsm +- and VDR Taq +-. After looking at his, his is not inverse. He and I take a Vitamin D3 supplement nearly every day, and it seems the only time my D3 absorbs from the sun is when I go to Florida on vacation and lay in the sun. I live in TX, and I can be in the sun a lot and for some reason, I've had to start (4 yrs ago after being diagnosed with Hashimoto's Thyroiditis) and keep taking a supplement.

The whole thing confuses me to no end. I am not sure what to do either. As long as I keep taking my D3, I do have a higher D3 count, that is all I know. If you find out anything else, please post it. Sorry I couldn't help you...I can't even help myself with the knowledge.

This is what I found on SNPedia as Yasko Methylation
https://www.snpedia.com/index.php/Yasko_Methylation

VDR Gene
rs1544410 - VDR Bsm (Risk Allele: T)
rs731236 - VDR Taq (Risk Allele: A)

VDR Taq TT --> AA +/+
VDR Taq tt --> GG -/-

So in Yasko Methylation, VDR Taq is opposite to Livewello : Risk Allele is A, not G as in Livewello

Am I getting this right????Lol

I don't know if this will contribute to understanding or if it will make everything worse, but here are my notes on VDR from the last time I tried to figure out the nomenclature. Source links included. I don't think the first is especially helpful to the purpose here, but I left it in for anyone who might have an interest.

http://www.ncbi.nlm.nih.gov/pubmed/23065592

VDR TaqI and VDR BsmI are associated with autoimmune thyroid disease. Decreased risk of AITD for the major allele of VDR BsmI (G) and the minor allele of VDR TaqI (C).

http://cebp.aacrjournals.org/content/18/11/2874.full
(See section entitled "DNA Extraction and Genotyping"

Based on standard nomenclature, genotypes for the four VDR variants, FokI (rs10735810), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236), were reported using lowercase and uppercase letters to reflect the presence or absence of a restriction site, which is consistent with the literature (FokI: T-f and C-F; BsmI: G-b and A-B; ApaI: T-A and G-a; and TaqI: T-T and C-t).

http://cebp.aacrjournals.org/content/15/12/2549.full
(See section entitled "Genotype Analysis")

Consistent with the literature, genotypes for the four VDR ... More

I don't know if this will contribute to understanding or if it will make everything worse, but here are my notes on VDR from the last time I tried to figure out the nomenclature. Source links included. I don't think the first is especially helpful to the purpose here, but I left it in for anyone who might have an interest.

http://www.ncbi.nlm.nih.gov/pubmed/23065592

VDR TaqI and VDR BsmI are associated with autoimmune thyroid disease. Decreased risk of AITD for the major allele of VDR BsmI (G) and the minor allele of VDR TaqI (C).

http://cebp.aacrjournals.org/content/18/11/2874.full
(See section entitled "DNA Extraction and Genotyping"

Based on standard nomenclature, genotypes for the four VDR variants, FokI (rs10735810), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236), were reported using lowercase and uppercase letters to reflect the presence or absence of a restriction site, which is consistent with the literature (FokI: T-f and C-F; BsmI: G-b and A-B; ApaI: T-A and G-a; and TaqI: T-T and C-t).

http://cebp.aacrjournals.org/content/15/12/2549.full
(See section entitled "Genotype Analysis")

Consistent with the literature, genotypes for the four VDR variants, FokI, BsmI, ApaI, and TaqI, are reported according to the standard nomenclature in which lowercase and uppercase letters represent the presence or absence of a restriction site, respectively. The FokI T and C alleles are represented by f and F, the BsmI G and A alleles by b and B, the ApaI T and G alleles by A and a, and the TaqI T and C alleles by T and t, respectively.

For ease in reference:

VDR variant Genotype Standard Nomenclature

VDR FokI T=*f* (minor allele)
rs10735810 C=*F* (MAJOR ALLELE)

BsmI G=*b* (MAJOR ALLELE)
rs1544410 A=*B* (minor allele)

ApaI T=*A* (minor allele)
rs7975232 G=*a* (MAJOR ALLELE)

TaqI T=*T* (MAJOR ALLELE)
rs731236 C=*t* (minor allele)

Edited to add:

That did not go well. The table gets squished when I save it. I hope it doesn't give you too much trouble.
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I see that this is a rather old post, so I don't know if my response will even get a reply or whatever. I haven't had my dna numbers sent to livewello, so I can't respond to anything there, but I have the same VDR bsm ++ TT and VDR Taq - - GG as the first poster above @RM5410. Reading the info from geneticgenie, it didn't really explain much, just that they were inverse. I am rather new to finding out my genes, so I have lots of questions. I am not very good at science, but I can pick up things quickly. Any ideas?

I'm on this as ++, but I see that it depens on if the scientists agree what a mutation is or isn't, so which A, C, T, etc. it belongs to. Some are even race-dependent. D vitamins are nothing to mess with if you ask me. Have your kidneys and the parathyroid functions checked before doing anything with that. It can suck calcium out of your bones or fry your kidneys if you mess with the wrong stuff.

I don't know Yasko's position, but would suggest looking at the material you're reading for a date. Possibly you're looking at something that was published 3-10 years ago and, as you know, the research is changing daily.
Tom Ballard, ND

RM-5410, thanks for posting Yasko's comments on the VDR SNPs. I had read that last year, but couldn't find it now. However, it doesn't totally clarify what her position is on SNP nomenclature. She is using T for "unrestricted" VDR taq and t for VDR taq with a "restriction site." I have always thought that upper case applied to the major (most frequent) allele and lower case applied to the minor (least frequent) allele. Not sure of the basis for that assumption, it may be comparable to the Livewello assumption, usually but not always true. All I know is that I am homozygous for the minor allele of both VDR Bsm and Taq, and I have achieved a 25OHvitaminD level of 60-70 ng/ml by supplementing with 10,000 IU of vitamin D3 per day. That may be a higher dose than most, indicating that maybe my VDR is not very well expressed. Also, I have no trouble taking in a high dose of methyl groups. My biggest difficulty arose with a high dose of folic acid and hydroxocobalamin, which combined with my compound heterozygous MTHFR status, caused me to be even more undermethylated than I normally ... More

RM-5410, thanks for posting Yasko's comments on the VDR SNPs. I had read that last year, but couldn't find it now. However, it doesn't totally clarify what her position is on SNP nomenclature. She is using T for "unrestricted" VDR taq and t for VDR taq with a "restriction site." I have always thought that upper case applied to the major (most frequent) allele and lower case applied to the minor (least frequent) allele. Not sure of the basis for that assumption, it may be comparable to the Livewello assumption, usually but not always true. All I know is that I am homozygous for the minor allele of both VDR Bsm and Taq, and I have achieved a 25OHvitaminD level of 60-70 ng/ml by supplementing with 10,000 IU of vitamin D3 per day. That may be a higher dose than most, indicating that maybe my VDR is not very well expressed. Also, I have no trouble taking in a high dose of methyl groups. My biggest difficulty arose with a high dose of folic acid and hydroxocobalamin, which combined with my compound heterozygous MTHFR status, caused me to be even more undermethylated than I normally would be and put me in bed for a week, and under the weather for 3 more weeks until I started taking a lot of methylfolate and methylcobalamin.

And the lack of standardization in SNP nomenclature is something all 23andme users run up against. Also, unless it's a GWAS, it's frequently hard to define what the risk allele for a given SNP is. Also, sometimes different alleles for a given SNP can increase the risk of different negative conditions. Less

Applying genetics to your health can be very frustrating because it's so new with many unknowns AND because it is only one piece of the three-legged stool. A person's health is reflected in their lab tests (including genetics), but also their health history and physical exam. It's easy to get caught up in treating the genes rather than the whole person - and this is encouraged by those selling drugs and supplements.

In my experience of doing comprehensive genetic reports over the years, VDR is very common, but not as important as other gene variations. When a patient of mine has a VDR SNP, I consider a serum vit D and calcium test and bone density. But even with this information there isn't necessarily a slam-dunk diagnosis, as blood will steal calcium from bones under acidic conditions and bone density problems won't show up until fairly advanced. If the person is still young, they won't know there's a problem for maybe decades.

That's where taking in the whole picture is important: is this patient also not exercising, therefor reducing bone formation? Do they eat a high sugar diet, which makes them more vulnerable ... More

Applying genetics to your health can be very frustrating because it's so new with many unknowns AND because it is only one piece of the three-legged stool. A person's health is reflected in their lab tests (including genetics), but also their health history and physical exam. It's easy to get caught up in treating the genes rather than the whole person - and this is encouraged by those selling drugs and supplements.

In my experience of doing comprehensive genetic reports over the years, VDR is very common, but not as important as other gene variations. When a patient of mine has a VDR SNP, I consider a serum vit D and calcium test and bone density. But even with this information there isn't necessarily a slam-dunk diagnosis, as blood will steal calcium from bones under acidic conditions and bone density problems won't show up until fairly advanced. If the person is still young, they won't know there's a problem for maybe decades.

That's where taking in the whole picture is important: is this patient also not exercising, therefor reducing bone formation? Do they eat a high sugar diet, which makes them more vulnerable to diabetes? Is there intake of magnesium low making them more prone to dozens of diseases including calcium deposits? Do they have genetic factors that make them more likely to have high oxalates which will bind to the calcium and form stones? Is there cholesterol low, therefore deficient in the oil that vit D is made from? Where do they live, how much are they outdoors and do they use sunscreen? . Etc, etc, etc.

Sometimes it's better to step back from chipping away at one tree and look at the forest.

Tom Ballard, ND Less

I found a text writting apparently by dr Yasko herself about VDR. She repaeatedly says that it is all very complicated and that there is disagreement. But she also says that low dose vit D + rosemary, sage and resveratrol are good for every geneotype.


Dr Amy Yasko:
"VDR information:

Recently there has been a barrage of questions related to VDR. The situation with respect to VDR is highly complex which is why I have not tried to thoroughly explain it in the past. I have tried to keep it simple for you and note the observed clinical relationship between those who cannot tolerate higher levels of methyl donors (tt) and those that can handle more methyl donors (TT) in terms of their Taq status. Based on the volume of questions and confusion regarding VDR I will go ahead and explain the complexity of the situation.

I believe this recent flurry of interest in the genotype designations for the VDR is related to of the use of GcMAF. While initially it was thought that the VDR SNP data played a role in determining the use of that agent, it has since been suggested that simply the use of Vitamin D may ... More

I found a text writting apparently by dr Yasko herself about VDR. She repaeatedly says that it is all very complicated and that there is disagreement. But she also says that low dose vit D + rosemary, sage and resveratrol are good for every geneotype.


Dr Amy Yasko:
"VDR information:

Recently there has been a barrage of questions related to VDR. The situation with respect to VDR is highly complex which is why I have not tried to thoroughly explain it in the past. I have tried to keep it simple for you and note the observed clinical relationship between those who cannot tolerate higher levels of methyl donors (tt) and those that can handle more methyl donors (TT) in terms of their Taq status. Based on the volume of questions and confusion regarding VDR I will go ahead and explain the complexity of the situation.

I believe this recent flurry of interest in the genotype designations for the VDR is related to of the use of GcMAF. While initially it was thought that the VDR SNP data played a role in determining the use of that agent, it has since been suggested that simply the use of Vitamin D may be a help. As such this focus on VDR may not be necessary. I had reached a similar conclusion with regard to vitamin D for my program a while ago with the additional caveat that I feel support for the receptors is also important. The bottom line is that I do feel vitamin D support is a positive, and the use of rosemary, sage and resveratrol can also help support healthy vitamin D levels.

First a quick point of nomenclature before I go in to the complexity of the situation. In general the presence of the restriction site is denoted by a lower case letter and the polymorphism that eliminates the site is denoted by an upper case letter. The situation is more complex in that the Bsm and Taq sites have an inverse relationship. To add to the confusion, studies have found decreased levels of VDR protein with Bsm BB and Taq tt genotypes compared to other genotypes yet vitamin D levels were significantly increased at the same time that levels of VDR protein were significantly decreased. Thus increased 1,25(OH)2 D3 levels, might lead to downregulation of VDR expression. Decreased VDR levels could result in defective VDR signaling.( JOURNAL CLINICAL IMMUNOLOGY Volume 29, Number 4 (2009), 470-478 )

The situation with Fok is also complex as the polymorphism (FF, loss of site) actually leads to the production of a protein with increased activity. The Fok SNP, situated in exon 2, gives rise to an alteration in the start codon position resulting in a 3 amino acid longer protein produced by the F allele. So the Fok site affects the protein directly such that those who are missing the restriction site (FF) make a shorter protein, but one that is actually more active. While those who do not have a mutation and have the restriction site actually make the full length protein but it has less activity.(Nutrition Reviews, What Are the Frequency, Distribution, and Functional Effects of Vitamin D Receptor Polymorphisms as Related toCancer Risk?Nicholas J. Rukin August 2007(II): S96 S101Vol. 65, No. . In conclusion, the Fok polymorphism yields a 424 VDR variant somewhat more active than the 427 variant in terms of its transactivation capacity as a transcription factor. (Uitterlinden et al. / Gene 338 (2004) 143 156)

The Taq and Bsm situation is even more complicated. Both are in a regulatory portion of the protein and the SNP changes do not affect the protein per se but they both affect a regulatory string of A s in the sequence. Thus the presence or absence of the Bsm and Taq sites affects the number of A s in the protein. Since Bsm and Taq have inverse effects both Bt and bT impact the number of A s. The number of A s in turn affects the stability of the information to make the VDR protein. 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."
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Tom, I alread did that. I am GG. But as YQ-1074 pointed out, researchers don't seem te agree upon wich allele is the risky one: A or G. So unfortunately, my raw data don't help. I've seen many online discussions in the mean time about Yasko treating this SNP differently then others do. But no one on those forums really understands what this all means for a specific genotype. I even came across a doctors website on which he/she argued that the SNP today actually is more common then the (formerly) wild type/good gene (thus: agreeing on this with Yasko) because we are overexposed to calcium nowadays. And less vitamin D would be helpful so that the excess calcium doesn't go where it isn't supposed to go (like on your arterial walls and in soft tissues). Another problem I come across is the inconsistency in nomenclature. e.g. a respectable German lab that does genetic research hasn't even heard of genes being indicated as an rs number. The dr I spoke to could not compare my gene report ot her knowledge base because of that.

So, I gues, it seems that my ... More

Tom, I alread did that. I am GG. But as YQ-1074 pointed out, researchers don't seem te agree upon wich allele is the risky one: A or G. So unfortunately, my raw data don't help. I've seen many online discussions in the mean time about Yasko treating this SNP differently then others do. But no one on those forums really understands what this all means for a specific genotype. I even came across a doctors website on which he/she argued that the SNP today actually is more common then the (formerly) wild type/good gene (thus: agreeing on this with Yasko) because we are overexposed to calcium nowadays. And less vitamin D would be helpful so that the excess calcium doesn't go where it isn't supposed to go (like on your arterial walls and in soft tissues). Another problem I come across is the inconsistency in nomenclature. e.g. a respectable German lab that does genetic research hasn't even heard of genes being indicated as an rs number. The dr I spoke to could not compare my gene report ot her knowledge base because of that.

So, I gues, it seems that my search for an answer ends here, for now.
BTW Livewello did respond to my question very quickly, and it corresponded with YQ-1074's point, that Livewello indicates the less comon genetype as +/+.

Here there answer:;


Re: I need help
Support (support@livewello.com) Add to contacts 2/1/2015 Keep this message at the top of your inbox

support@livewello.com


Thank you for contacting us.

If you look at the bottom of each report you will see a section that describes how LiveWello computes your gene variance results. We use the same method for every singe SNP in the standard report. What the software does is compare a SNPs minor allele frequency (MAF) with your genotype for that SNP. So for instance if your genotype is GG and the MAF if G, you will be +/+. If the MAF was T, you would be
-/-.

These MAF values are obtained from NCBI's dbSNP and 1000Genomes, which are internationally recognized genetic reference databases. You can verify the minor allele for each of your SNPs by clicking on the value in the minor allele column of your report.

This is the dbSNP entry for VDR Taq:
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs731236


And here is the entry for VDR Bsm:
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs1544410

If you have any further question don't hesitate to contact us.


Warmly,



Customer Support,

Livewello LLC. Less

Just remembered, that VDR is an upregulated gene, may thats why Yasko is treating it differently.

Same here

Again, When in doubt, go to the source. Look at your 23andme raw data. It will also link you to research. If you don't know how, here's a video that explains how to do that. https://www.youtube.com/watch?v=rNK_vZu9qDA.

The question is, if only VDR is 'switched/bad/good' or whatever, or other genes may be questioned as well? As we do have as base for comparison only Yasko report from here/LW compared to Yasko/knowyourgenetics - is the only one black-sheep.....

Just noticed the same with VDR.

You are probably GG for rs731236, as I am. G is the minor allele for this SNP, with a global frequency of 0.2766. Livewello assumes that the minor allele is always the risk allele, so they have you as +/+. On the other hand, Geneticgenie follows Yasko, and she thinks the risk allele is the major allele, A, so she and Geneticgenie have you as -/-. Your alleles haven't changed, but the risk allele is different between the two sources. I think that Yasko is probably right, the minor allele is usually but not always the risk allele. I assume that she has studied the issue and has a basis for her opinion, whereas as far as I can deduce, Livewello just makes the blanket assumption that minor=risk, and I think that's an oversimplification. There is a discussion of this issue with this SNP on Yasko's website if you can find it.

When in doubt, go to the source. Look at your 23andme raw data. Here's a video that explains how to do that. https://www.youtube.com/watch?v=rNK_vZu9qDA

There is a way to manually confirm your results for LiveWello but I don't know about the other companies. LiveWello gets your phenotype by comparing your genotype with the minor allele of a SNP. These minor alleles can be found at dbSNP. So to manually verify your result, look up the minor allele on dbSNP and see how it matches against your LiveWello result. You should write all 3 companies then post their answers here so all can learn about this important question.

I suggest you ask both companies about this discrepancy. You are not the only one that has noticed these discrepancies and it would be nice to post their answers here for everyone to see.