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ACAT/CBS/MTFR Recommendations

Messages
17
Here are my GeneticGenie results :

Homo (+/+) for
VDR Bsm, CBS A360A

Hetero (+/-) for
ACAT1-02, MTHFR C677T, MTHFR A1298C, MTRR A66G, MTRR H595Y, MTRR K350A, CBS C699T

Prior to a few years ago, I was pretty healthy. Then I had a massive candida issue (think I was exposed to some virus/bacteria/toxin that triggered it) and from that point on I have had gut issues (dysbiosis/yeast) and food intolerances (gluten, dairy). I have been doing 90% paleo for a while now and that helps. Last week, on vacation, I cheated on my diet and now my gut is a mess. LOL. I plan on doing a very strict form of paleo and take some pro-gut supplements to fix that. Then I want to start addressing my MTHFR issues as I am compound hetero MTHFR. Anyone have any recommendations on how to proceed for compound MTHFR?
 
Messages
15,786
Homo (+/+) for
VDR Bsm, CBS A360A

Hetero (+/-) for
ACAT1-02, MTHFR C677T, MTHFR A1298C, MTRR A66G, MTRR H595Y, MTRR K350A, CBS C699T
VDR Bsm is reported backwards, so you have the good version. CBS A360A has no impact on the function of the CBS gene, and ACAT1-02 has no impact on the function of the ACAT1 gene.

MTHFR C677T + A1298C, when both heterozygous, are about as bad as having MTHFR C677T homozygous. So your methylfolate production might be running at about 30% of normal. Thus methylfolate supplementation is strongly indicated. You also might need to avoid folic acid supplementation (in vitamins or fortified foods) to get the most benefit from methyfolate.

Your MTRR SNPs probably aren't having a big impact on MTRR gene function, especially since they're all heterozygous, but you do have several of them. Hence supplementing methylB12 seems like it would be a good idea. Since you have the faster versions of COMT and MAOA, methyl- supplementation shouldn't present a problem itself, but watch out for potassium depletion if you try high doses of methylB12.
 
Messages
17
Also, I am not sure what you mean by VDR Bsm being reported backwards. The VDR Bsm risk allele appears to be T and I am TT and show red on both Genetic Genie and Sterling's Report. Am I missing something?
 
Messages
15,786
Also, I am not sure what you mean by VDR Bsm being reported backwards. The VDR Bsm risk allele appears to be T and I am TT and show red on both Genetic Genie and Sterling's Report. Am I missing something?
VDR Bsm and VDR Taq are linked SNPs. That is, if you have a certain result in one, you know what you have in the other one. For some reason the "risk" is listed as being the opposite versions. Thus anyone -- for Taq is ++ for Bsm, and vice versa. From what I've read, the riskier version is Taq ++, which correlates to Bsm --, and results in lower vitamin D 25.

It also looks like Yasko removed Bsm from her test at some point, so I guess she got the memo on that one :p Not sure why geneticgenie still reports it at all, though.
 

Bluebell

Senior Member
Messages
392
Also, I am not sure what you mean by VDR Bsm being reported backwards. The VDR Bsm risk allele appears to be T and I am TT and show red on both Genetic Genie and Sterling's Report. Am I missing something?

For VDR Bsm, I think that Yasko does not report that one backwards*. As far as I know, she goes along with the view of +A / -G, which is the conventional view.

In terms of 23andme reporting, the G is a C, so GG or CC is -/- and that is the result of the majority, which is what Yasko apparently says also.

The A on 23andme is a T, and AA or TT is +/+ which is the result of the minority, and considered a risk, which is apparently what Yasko says also.
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Yasko apparently reports VDR Taq backwards. Conventionally, it is +G / -A, AA is the majority allele, which in conventional terms would be denoted -/-, but instead she says it is +A / -G and calls AA +/+, the risky allele.

It shows up in the following chart that she is calling a VDR Taq of C (G) to be a -/- even though that's the minority result : http://geneticgenie.org/blog/.

GeneticGenie says in that blog post above that he was reporting it the conventional way until January, when he decided to go with the Yasko way and flip it.
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Therefore, for VDR Taq, if you have a -/- and GG on the Genetic Genic report, actually you have the minority result which conventionally would be denoted as +/+.
For VDR Bsm, if you have a +/+ and AA or TT on the Genetic Genie report, you really do have the minority result there.
So on both those Vitamin D Receptors, you appear to have the minority version.

In an earlier thread (http://forums.phoenixrising.me/index.php?threads/my-yasko-snps.24228/#post-371019), Valentijn said that the minority version of VDR Taq, GG, might be the more protective one, and maybe that's why Yasko designates the minority one as -/-. From what I've read, the majority version of it, AA, the one that Yasko calls the risky one and +/+, which is the one that I have, helps in several situations regarding my other mutations, so I don't think it is that harmful.

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* Note that my understanding of this is based on my research of a couple of months ago now (so maybe something has changed in the meantime), and I did not order the Yasko analysis myself, so it's only from what other people on the internet have written about her analysis, although they did post what their Yasko results were and they were all consistent with this. I really don't know much about it, and I could be wrong, although I think that my interpretation here is correct. Please let me know if I am wrong about the two VDRs and how Yasko handles them!
 

Bluebell

Senior Member
Messages
392
Anyone have any recommendations on how to proceed for compound MTHFR?

Zenmaster, I am also compound heterozygous MTHFR. Of all the permutations of those 2 main MTHFR SNPs, having them both as heterozygous is the second worst combination for health. (The worst one is homozygous C677T.)

Personally, I think that I was having a big problem with artificial folic acid and artificial B12 cobalamin that I didn't realize, but which was causing a lot of symptoms. I stopped all supplements with artificial folic acid, and stopped eating foods that were fortified with it, and some of my most visible physical symptoms got better in only 2 months, which gives me hope that some of my other symptoms can also be lessened with the continuing avoidance of artificial folic acid (and artificial B12).

Adding in "real" folate and "real" B12 to my intake is another step to take, and I'm just about to start that.

I can't give any more thoughts than this about compound heterozygous MTHFR, because I do not know much about biochemistry. :confused:

To learn more about this issue generally, you can have a look at the external links that are in the info list that I've compiled - the thread is linked to below in my signature line.
 
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15,786
In an earlier thread (http://forums.phoenixrising.me/index.php?threads/my-yasko-snps.24228/#post-371019), Valentijn said that the minority version of VDR Taq, GG, might be the more protective one, and maybe that's why Yasko designates the minority one as -/-. From what I've read, the majority version of it, AA, the one that Yasko calls the risky one and +/+, which is the one that I have, helps in several situations regarding my other mutations, so I don't think it is that harmful.
From what I've read in various papers, Bsm CC (GG) results in lower D 25, as does Taq AA (TT). Though maybe lower D 25 means faster VDR function, if the VDR is taking up the D 25? It might be similar to the COMT situation, where "bad and good" are inappropriate simplifications, and the reality is that one is faster and one is slower, and each is associated with various risks.
 
Messages
17
From 23AndMe, I have :

VDR BSM (TT)
VDR TAQ (GG)

In snpedia for Yasko Methylation it has :


Though the GeneticGenie blog does not clear it up very well as they imply with the examples that VDR Taq GG is the good one. Sigh. Still not sure what I have in regards to VDR.
 

Bluebell

Senior Member
Messages
392
From what I've read in various papers, Bsm CC (GG) results in lower D 25, as does Taq AA (TT). Though maybe lower D 25 means faster VDR function, if the VDR is taking up the D 25? It might be similar to the COMT situation, where "bad and good" are inappropriate simplifications, and the reality is that one is faster and one is slower, and each is associated with various risks.

For me, there are two points:

Point 1. What is Yasko backwards on? (She is spoken of as presenting one of the two VDR results, Taq and Bsm, unconventionally.) There seem to be two possibilities (and perhaps she is backwards on both of them!)

1a. It appears, to me, that she is backwards on how she presents VDR Taq. My perception is that she says that the VDR Taq genes that the majority of people have are the less-healthy ones and are to be denoted as "+/+", whilst "+/+" does not appear to be the way other genetic experts denote the genetic result of the majority. My definition of "backwards" here is that she is being backwards about calling a "+/+" a "-/-", and calling a "-/-" a "+/+".

1b. She may also take the result of either VDR Taq or VDR Bsm, if she only tests for one of them and not for both of them, and flip the result of the one she tests for around (in terms of the corresponding letters), then say that the mirror image is the result of the VDR SNP that she does not test for, in order to present both SNPs in the patient results. That is another meaning of the word "backwards" - she is presenting one result as identical to the other one, except that it is backwards (in terms of the corresponding letters).
I sort of recall reading that she may have done this at one point, and perhaps these days she only presents the one result that she does test for, and leaves the other SNP off; but I don't really remember.
If she did/does this, I guess that it is not a completely accurate way of determining the results of those 2 SNPS (just substituting a mirror image of the one known one for the other unknown one) because it seems that not everyone has those Vdr and Bsm SNPs in mirror images of the other: I read in another thread here last night where Valentijn mentioned that she had run across 3 people this week who did not have the mirror image result in Bsm and Taq.

Point 2. There is a larger question of whether "+/+" and "-/-" are always meant to indicate the minority result and the majority result, in terms of incidence in the human population (or in terms of a specific ethnic or regional population),
OR if they are meant to indicate what is riskier ("+/+") and safer ("-/-") to our health in our modern "western" lives.

My impression is that the conventional scientific notation is for "+/+" to mean the less-frequent result and "-/-" to mean the more-frequent result in a population. But my impression is not based on much scientific background information, so I may be incorrect. I do know that this is how GeneticGenie first displayed the results of VDR Taq, before changing it to the Yasko notation in January because people who used both the GeneticGenie and Yasko analyses were getting confused about VDR Taq.

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. If Yasko is going against convention just for that one SNP, I think she should make this clear every time she mentions that SNP, or use a different kind of notation there (such as ">/>" or something) so that it's obvious what her message is.
 
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15,786
My impression is that the conventional scientific notation is for "+/+" to mean the less-frequent result and "-/-" to mean the more-frequent result in a population. But my impression is not based on much scientific background information, so I may be incorrect.
Frequency isn't particularly relevant, so +/+ should be the risk-associated genotype. It's not uncommon for the less common genotype to be the better version

I'm also pretty sure Yasko isn't using the more/less frequent status as a major determinant in marking SNPs as +/+. For example, the MAOA has the much more common version marked as being +/+ (one reason I like to refer to it as the "slow" version, not the "bad" version).
 

Bluebell

Senior Member
Messages
392
From 23AndMe, I have :
VDR BSM (TT)
VDR TAQ (GG)
In snpedia for Yasko Methylation it has :
rs1544410 - VDR Bsm (Risk Allele: T)
rs731236 - VDR Taq (Risk Allele: G)

Though the GeneticGenie blog does not clear it up very well as they imply with the examples that VDR Taq GG is the good one. Sigh. Still not sure what I have in regards to VDR.

Zenmaster, I think there are two aspects of this:

1. What are your results, in terms of how often they occur in the population?
You have the minority result for both of those VDR SNPs. That is clear: you can look at the US government website for genetic data, and see that your results are the minority results.
Does having a less-common mutation mean that there is something wrong with your SNP? No. Does it mean that your SNP result is less healthy than the majority's result? No. Your minority SNP result might be healthier than the majority's.

2. What do your results mean? Does Yasko think that these are beneficial to your health, or detrimental? Do other doctors and researchers think that these are beneficial to your health, or detrimental?
It is clear that Yasko thinks that one of your minority VDR results, the VDR Taq, is actually a good thing for your health, a "-/-" in her analysis. She thinks the other of your minority VDR results, the VDR Bsm, is a bad thing for your health, a "+/+" in her analysis.
Do other researchers/doctors think the same as Yasko about those two minority VDR results? I don't have a clue. They may or may not.
 

Bluebell

Senior Member
Messages
392
I'm also pretty sure Yasko isn't using the more/less frequent status as a major determinant in marking SNPs as +/+. For example, the MAOA has the much more common version marked as being +/+ (one reason I like to refer to it as the "slow" version, not the "bad" version).

In my chart for my own results (which I did about 2 months ago, by hand, so there could be inaccuracies in it), I have this for MAO A, which did not appear to me at the time to go against either the real population incidence or Yasko's notation:
MAO A
R297R
Rs6323
possibilities: +T/-G
major alleles: G
my alleles: TT
my result: +/+

So, is it the case that my TT is the majority result and not the minority result? Or does Yasko call TT a "-/-" and consider it good?
 
Messages
15,786
So, is it the case that my TT is the majority result and not the minority result? Or does Yasko call TT a "-/-" and consider it good?
G is definitely the less common allele (though not at all uncommon). And she also marks TT as the +/+ version. A non-race-specific American sample of 4550 gives 66% with TT and 11% with GG.
 

Bluebell

Senior Member
Messages
392
G is definitely the less common allele (though not at all uncommon). And she also marks TT as the +/+ version. A non-race-specific American sample of 4550 gives 66% with TT and 11% with GG.

Okay, so the part that I got wrong in my chart for MAO A was calling G the major result - it is the minor result in "Europeans", although it's the major result in some populations, such as "Asians":
http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=6323.

Venterbell, as usual, follows my lead with his TT. :snigger:

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Are MAO A and VDR Taq the only 2 where Yasko reports the majority as having the more-risky/less-healthy results? Or does she do that a lot?

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Does anyone else use these blasted plusses and minusses in their SNP notations, or is it mainly a Yasko thing (including reports that seek to resemble hers)?

...I did a search on Yahoo to try to answer that, though I must say the first batch of results were not what I intended! http://images.search.yahoo.com/search/images?_adv_prop=image&fr=ie8&va=mao a +/+

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My second Yahoo search did find for me a previous explanation on PhoenixRising about Yasko and her VDR Taq notation, where even Greenshots was a bit impatient with Yasko:
http://forums.phoenixrising.me/index.php?threads/dr-vank-the-vdr-changes.18858/

Quote from Yasko:
"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."

So on my chart, I'm gonna keep callin' my VDR Taq AA result a "-/-". :D