The Great VDR Taq/Bsm Debate

[npeden]

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

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.

 

[npeden]

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.

Ok, sort of new here so not sure who I should address this to but I would very much like some help. I am highly mutated, especially in my neurotransmitters. I take passion flower tincture (harmaline) for my MAO A that I saw someone above mention.

As for my VDRTaq, I don't have Taq. My VDR bsm is +-CT. I have been told that this can impact my COMT H62H TT ++. I know COMT upregulates dopamine but I actually find that taking tyrosine helps my depression...I have TH GG which nutrahacker (ya I know, not real respected source) says gives me low dopamine. Maybe that is why I can take it.

So any thoughts on VDR bsm +-CT? Somewhere in this I read that it was somehow unique. And I notice in your posting that I am replying to says generally VDR bsm is not problematic. And I like the idea of testing calcium instead of vit. D. Great idea.

I have my vit. D tested regularly and I take 5k mg. a day. I have CaSR AG which nutrahacker says over produces calcium. So I take vit. D cautiously and I take a ton of magnesium to reduce calcium.

Thanks for any help.

 

[Sushi]

I have my vit. D tested regularly and I take 5k mg. a day. I have CaSR AG which nutrahacker says over produces calcium. So I take vit. D cautiously and I take a ton of magnesium to reduce calcium.

You can also test Vit D 1,25 which gives you a good idea of whether calcium is going to be a problem. Most docs just test Vit D 25.

Sushi

 

[npeden]

You can also test Vit D 1,25 which gives you a good idea of whether calcium is going to be a problem. Most docs just test Vit D 25.

Sushi

Thanks, Sushi. Will try for that instead of Vit. D 25.

 

[Valentijn]

@npeden VDR Bsm +/- (rs1544410 CT) is extremely common. 40-50% of every population has that version. And having Bsm +/- means that you almost certainly have VDR Taq +/- as well.

It's a bit more interesting if Bsm and Taq don't much up, but that is very rare. For example, if Bsm was +/- and Taq was -/-, etc.

 

[npeden]

Geez, you are bright, Valentinjin! Sterlings App has no taq but promethease has two at least:

"Rs708272, also known as the TaqIB polymorphism of the CETP gene, may influence the levels of the "good" cholesterols, the high density lipoprotein (HDL) cholesterols. Generally, the B2 allele is considered to lead to higher HDL levels.
However, high HDL cholesterol, at least when combined with another HDL raising SNP (rs1800588), doesn't appear to actually protect individuals from coronary artery disease, at least based on one study of ~800 Caucasian male patients. [PMID 18164013] This is MINUS.

(I have hi risk of coronary heart disease; I take fish oil 3 g. and Natto Max 2000 fu daily.)

"rs1800497, a SNP also known as the TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene (even though it is actually located over 10,000bp downstream of the gene), gives rise to the DRD2*A1 allele. This allele (rs1800497(T)) is associated with a reduced number of dopamine binding sites in the brain [PMID 9672901], and has been postulated to play a role in alcoholism, smoking, and certain neuropsychiatric disorders. This is MINUS.

I have a lot of trouble with dopamine. I have COMT to worry about and I have dopamine (and others) oxidized by MAO A for which I take passion flower tincture. It works well.

VDR down regulates dopamine. COMT upregulates it. I have been taking tyrosine because I feel like it gives me a sense of well being, only slight, but noticeable. I take a lot of NAC to over ride candida and provide glutathione ( I am c677t for MTHFR) and I feel like the NAC "dampens" the tyrosine.

But a friend, who I respect, suggests I drop the tryrosine since I had a very bad few days of terror recently. What do you think?

Got any suggestions what to do with this all? I am very confused right now.

Thanks for your help.

 

[Valentijn]

@npeden - "Taq" isn't a label specific to the VDR gene. Basically it's just terminology describing how that particular SNP is located. Hence VDR Taq has nothing to do with CEPT Taq or DRD2 Taq.

No idea regarding tyrosine. But if something is causing unpleasant side effects, stopping it usually is a good idea, unless your doctor has a good reason for you to stay on it.

 

[npeden]

So, this means I do NOT have VDR taq?

 

[Valentijn]

So, this means I do NOT have VDR taq?

The SNP called VDR Taq is identical to VDR Bsm. Hence you're probably +/- for both. And neither of them have much impact, so I wouldn't worry about it.

 

[npeden]

Well, that made my day. Thanks, Valentijn.

 

[npeden]

Ok, here is another twist. I am VDR Bsm rs1544410 CT +/- BUT I am also HPA axis / Endocrine rs1042636 CaSR A AG: 1/2 so I have too much calcium. I take a lot of magnesium to reduce it but I am finding out that calcium is in a lot of things. I had been using chammomile tea but it contains Vit. D so will switch to peppermint.

I am about to have my Vit. D tested for the umpteenth time but this time we are going to do a Vit, D 1, 25 test that I think Valentij or Caledonia here recommended. This, I hope, will tell me how much Vit. D is adding to my calcium.

And thoughts on this, Methyl Health and others? Thanks, np

 

[picante]

I ran across this link on another Vit. D thread. Does anyone know where they got their information? I'm curious, since I've got +/+ VDR Bsm and high D1,25 levels. This is the first time I've seen the claim that those with the mutation would tend to over-convert.

http://resqua.com/702188759/what-info-is-available-about-vdr-bsm-gene

VITAMIN D Receptor BSM Single Nucleotide Polymorphism [SNP] and AUTOIMMUNE DISEASE

PICTURE: Vitamin D Receptor BSM1 [A60890G]

Most doctors don't check for Vitamin D 1,25 because it’s half-life is so very short and the doctors were generally taught in medical school not to bother checking Vitamin D1,25 levels.

People with the Vitamin D Receptor mutations called VDR BSM end up readily converting their vitamin D to D1,25 and meanwhile their Total Vitamin D 25 appears to be low [because it is all getting converted to D 1,25, and their doctors aren’t checking their Vitamin D1,25 levels] And so, the doctor doesn’t realize that although their patient’s Total Vitamin D appears to be too low, in reality they have plenty of Vitamin D in the active form of Vitamin D 1,25.

 

[Valentijn]

I ran across this link on another Vit. D thread. Does anyone know where they got their information? I'm curious, since I've got +/+ VDR Bsm and high D1,25 levels. This is the first time I've seen the claim that those with the mutation would tend to over-convert.

http://resqua.com/702188759/what-info-is-available-about-vdr-bsm-gene

I'm not sure why that blog or whatever is interesting. It seems to be someone's very brief and basic opinion with absolutely no citation to any sources.

 

[picante]

That's what I thought, @Valentijn. Meanwhile, I found more information on this site: http://ephysiologix.com/vitamind/
(I don't really know what a "biohacker" is, but there is a list of references.)

VDR Bsm

If a person has a mutation in VDR BSM there is an up regulation in the conversion of 25(OH)D to 1,25(OH)D and so their total 25(OH)D appears to be low because it is all getting converted to D 1,25. The labs will show low levels of 25(OH) vitamin D yet the person will actually have optimal levels of the active form, 1,25D. Supplementing too much Vitamin D in this situation can lead to toxicity and increased risk for autoimmune disease.

And a discussion of ratios:

The ratio of 1,25(OH)D to 25(OH)D should be 1.3-2:1. One thing to remember is that 25(OH)D is reported as ng/ml and 1,25(OH)D is reported as pg/ml so the ratio is based on the 1000 fold difference mentioned earlier. An imbalanced ratio indicates the presence of an underlying problem and could be due to several factors. If your 1,25(OH)D is on the high side of the range and your 25(OH)D is normal or low this is not a favorable situation. This increased ratio could be due to infectious pathogens and/or high pro inflammatory cytokines. Infections, inflammation and autoimmune process tend to up regulate the conversion of 25(OH)D to 1,25.

My ratio was 1.93 in Jan. after a month+ on 3000 IU transdermal vitamin D3.

(Actual readings were 103.1 for 1,25 dihydroxy and 53.4 for 25-hydroxy)​

My ratio was 1.79 at the end of March after stopping D supplements in January.

(Actual readings were 61.2 for 1,25 dihydroxy and 34.1 for 25-hydroxy)​

That put me barely under the top of the range for 1,25 and barely over the bottom of the range for 25-OH.

I started supplementing 1000 IU every other day (orally) just to see if I would feel better. And I added in vitamin A twice a week. I've never taken it before.
But I'm lost at sea with vitamin D.

 

[Valentijn]

That's what I thought, @Valentijn. Meanwhile, I found more information on this site: http://ephysiologix.com/vitamind/
(I don't really know what a "biohacker" is, but there is a list of references.)

Oddly, the one thing which they don't cite to is any source for their claim regarding Bsm

 

[btdt]

I have
VDR Bsm rs1544410 TT +/+
VDR Taq rs731236 GG -/-

I have a brother who had rickets not sure if that means anything or not. I have had a problem with supplementing vit D and calcium dr ordered after I easily broke my foot... the reaction was pounding heart light headed and two fire balls in my eye 30 min after taking 400mg of vit d and I can't recall the amount of calcium...

I was sent to a kidney dr for 24 hour urine told to take vit D 400mg for a month and to do another 24 hour urine after a month...
I tried after 3 days I was unnerved with repeating songs in my head and less sleep than normal 4th day of 4000mg vit D I did not sleep a wink thoughts were scrambled. I stopped the Vit D tried to call the doc was told she was gone for a months vacation. I tried to take the vit D few days on few days off for that month.
End of the month my vit D was was lower then it had been before I supplemented Vit D... doc was uninterested in my sleep issues said keep taking the vit D ... and that was all.

Of course I have not taken vit D since as I like to sleep.
Not sure what the problem is but it seems whatever it is I am not going to get any help from a kidney specialist.

Is there a glaringly obvious issue with this genetic profile that is obvious to a person here?

I took my lower vit d after a month of mostly taking vit d a sign the more vit d I take the more my body will dump as it does not want it... and I felt bad taking it.
any ideas?

Same brother was also born with grand mal seizures and mostly blind...I have no idea of his genetics...

I test deficient for vit D not sure which test

 

[picante]

Hi, @btdt, given your reactions to D supplements, perhaps it would be good to request a test for both 1,25(OH)D (calcitriol) and 25(OH)D (calcidiol).

From my post above:

If your 1,25(OH)D is on the high side of the range and your 25(OH)D is normal or low this is not a favorable situation. This increased ratio could be due to infectious pathogens and/or high pro inflammatory cytokines. Infections, inflammation and autoimmune process tend to up regulate the conversion of 25(OH)D to 1,25.

I still have a high ratio, and have not been able to tolerate supplemental D3, even though my 25(OH)D is down in the bottom of the range. My ND has me try it periodically, and I've tried both caps and drops (transdermally and sublingually). For me, it triggers immune activation symptoms, which also happen to be my post-exertional symptoms. That makes me think that it's my EBV and HHV-6 infections that are the source of the high calcitriol, as they claim above.

 

[alicec]

Is there a glaringly obvious issue with this genetic profile that is obvious to a person here?

No, those SNPs are very common and have a negligible effect.

 

[btdt]

@picante Does the EBV have to be active to cause high calcium or just be in my body? last test it was not active but I have had times of high inflammation and tend to be chasing down one infection after the other so both make sense. I think my doc is past the point of looking at this point and has given up on me. I could request more tests and likely get it just wonder if it is worth the bother. I can just as easily take your word for it and move to the next row of issues... possible answers only old and tire people would get that comment likely thanks for the help.

 

[picante]

Does the EBV have to be active to cause high calcium or just be in my body?

I don't know; I've never made that connection. I assume you must be talking about high calcium in the bloodstream. I really get lost about blood levels of minerals, as they don't seem tell us much about tissue levels.

Or did you mean calcitriol? (1,25-D). I think the article is saying that any infection or autoimmune process would increase conversion of calcidiol to calcitriol. Do you have an autoimmune condition?

I also get lost in the debate about what constitutes proof of an active EBV infection. Mine is in my CNS. Doctors have been very careful to tell me that although PCR testing on cerebrospinal fluid for viral particles might reveal such an infection, lumbar puncture may be too invasive a procedure for me. Their skepticism about it is attenuated by my EBV & HHV-6 antibodies being 30X the upper limit of the range. And my response to antiviral medication also seems to convince them. My evidence for the infection is my post-exertional immune activation -- you know, symtpoms! Very much the symptoms I had with EBV meningitis, only without the delirium, vomiting, and rash.