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When "Common SNPs" Matter

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
Short video,2 minutes, where Dr. Steven Zeisel explains; "We are reporting how there common SNPs change whether you need choline or not".

http://epigenie.com/snps-nutrition-and-dna-methylation-with-dr-steven-zeisel/

So can we end the "it's common so it does not matter" debate and get on with getting better?

Here is the Transcript:

Well, we think that there are a number of genetic variants, single nucleotide polymorphisms. I’ll call them SNPs. These SNPs are extremely common in one carbon metabolism, especially among Caucasians. And we are reporting that these SNPs dramatically change whether you need choline or not, and that people who have these metabolic inefficiencies related to these snips are on the order of 25 to 85 times more likely to develop liver and muscle damage when deprived of choline. And I think they’re also the people who are going to be more sensitive to making epigenetic modifications. Because they can’t either make choline, or they use it faster and they don’t have as much for methyl groups to do methylation with. One of these genetic variations turns out to be in a gene that makes choline from scratch in the liver. It’s called PEMT. And that gene methylates phospholipid to form phosphatidylcholine and thereby choline. It turns out that gene is turned on in young women by estrogen. It’s there probably to get them through pregnancy where they have to deliver huge amounts of choline to build a good fetus. And about half the population in North Carolina has a genetic variant, a SNP in that gene, that makes them unresponsive to estrogen. And so they reduce to the sad state of men and can’t make extra choline during pregnancy. So that probably makes those women and their babies the most susceptible to variations in choline and methyl groups during pregnancy, and probably to some of these epigenetic phenomenon that we’re looking at in terms of brain development.
 
Last edited:
Messages
10
Thanks for the link to Dr. Steven Zeisel, MD and his explanation about who might really benefit from 'choline' (or not) and the related PEMT snps.

What are good choline and lecithin choices to supplement with? I rely on food (runny organic eggs) to provide my 'choline'.

With a past history of breast cancer (hormonal ie estrogen positive) and knowing supplemental 'lecithin' is usually soy-based I'm wary to take even a non-GMO soy-based supplement.

Any comments from those who have researched this or received recommendations from a practitioner?

My PEMT (per MTHFRSupport Variant Report v2.0):

rs7946 PEMT G634A T CT +/- (hetero)
rs4646406 PEMT T17020543A A AT +/- (hetero)
rs4244593 PEMT T17023592G T GG -/- (good)


thanks,
a Canadian
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
@ppodhajski This is very interesting to me, and I’ve spent a while looking into my snps. I do have a question or two which you may be able to address, and, in any case it’s entirely possible that I’ve gotten something wrong here…

So, 23andme has 41 SNPS on my PEMT gene, all but two of which are homozygous. Promethease lists only 5 variants, for whatever reason. Those pulled out by MTHFR Support are the three @victoriana mentioned above. Interestingly, Yasko calls out the rs4646406 snp and refers to it as a “2nd Priority” snp, one that ought to be addressed. I am homozygous AA, according to 23andme, the “Risk” allele. But Promethease lists me as TT, and its favorability is “Not Listed.” Can you clarify what appear to be common discrepancies of these two reports? I think I missed something in genetics 101!

Also, rs4646406 has a couple of related articles linked to SNPedia, one with associations of folate and choline metabolism and another with endometriosis-associated infertility.

Just as a point of interest, my mother had endometriosis and ultimately went on to have 9 pregnancies and 5 live births.

On the other hand, she also died of breast cancer at the age of 59. She was ahead of her time, totally into supps, the Gerson diet and so on and so forth and I remember her talking about choline.

Apropos of this, I found rs7946 most interesting. Promethease links to SNPedia show studies related to fatty liver for people who overeat, actual individual need for choline and choline metabolism and risk of breast cancer. Finally, there is a study that suggests an influence of biomarkers for choline metabolism when folate intake is restricted. My recent NutrEval and Oat tests show difficulties with folate metabolism, I suspect at least partly related to all my MTRR snps.

Oh, and I have high cholesterol. Given the liver stuff, does that have anything to do with this? Or, should I go back to the folded-protein thread, where there seemed to be some connection with cholesterol levels!

There’s way too much information for my brain to handle!!! Ph-f-f-f-f-t-t-t, s-i-z-z-l-e!

Oh, and one more thing, I spent quite some time perusing your selenium thread last week and almost got a post prepared when I sizzled out. Is there only one selenium thread? The one about the nutrigenomics of selenium? Or have I lost track of one?

I do still have more questions…

Thank you!!
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
@ppodhajski This is very interesting to me, and I’ve spent a while looking into my snps. I do have a question or two which you may be able to address, and, in any case it’s entirely possible that I’ve gotten something wrong here…

So, 23andme has 41 SNPS on my PEMT gene, all but two of which are homozygous. Promethease lists only 5 variants, for whatever reason. Those pulled out by MTHFR Support are the three @victoriana mentioned above. Interestingly, Yasko calls out the rs4646406 snp and refers to it as a “2nd Priority” snp, one that ought to be addressed. I am homozygous AA, according to 23andme, the “Risk” allele. But Promethease lists me as TT, and its favorability is “Not Listed.” Can you clarify what appear to be common discrepancies of these two reports? I think I missed something in genetics 101!

Also, rs4646406 has a couple of related articles linked to SNPedia, one with associations of folate and choline metabolism and another with endometriosis-associated infertility.

Just as a point of interest, my mother had endometriosis and ultimately went on to have 9 pregnancies and 5 live births.

On the other hand, she also died of breast cancer at the age of 59. She was ahead of her time, totally into supps, the Gerson diet and so on and so forth and I remember her talking about choline.

Apropos of this, I found rs7946 most interesting. Promethease links to SNPedia show studies related to fatty liver for people who overeat, actual individual need for choline and choline metabolism and risk of breast cancer. Finally, there is a study that suggests an influence of biomarkers for choline metabolism when folate intake is restricted. My recent NutrEval and Oat tests show difficulties with folate metabolism, I suspect at least partly related to all my MTRR snps.

Oh, and I have high cholesterol. Given the liver stuff, does that have anything to do with this? Or, should I go back to the folded-protein thread, where there seemed to be some connection with cholesterol levels!

There’s way too much information for my brain to handle!!! Ph-f-f-f-f-t-t-t, s-i-z-z-l-e!

Oh, and one more thing, I spent quite some time perusing your selenium thread last week and almost got a post prepared when I sizzled out. Is there only one selenium thread? The one about the nutrigenomics of selenium? Or have I lost track of one?

I do still have more questions…

Thank you!!

Yes, I think there is only one selenium thread but we talked about it in another as well, the one on UPR I think?

First for the cholesterol, look up your MYRF gene. rs174537. T is the slow allele which leads to lower cholesterol/ I finally have a good one on this (T,T) but I am afraid it leads to my nerve damage.

Most of the PEMT SNPs studied by Dr. Zeisel are not listed in 23andme. He has some others you can look at though.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574369/

I am homozygous for BHMT rs3733890 (AG). This will slow down production of SAM and it is where PEMT gets the methyl group to assist the PEMT enzyme.

You can either find ways to speed up BHMT (Zinc is a cofactor) or eat more eggs. There is no vitamin cofactor for PEMT.

http://www.hindawi.com/journals/tswj/2013/931626/fig2/

931626.fig.002.jpg
 
Messages
15,786
First for the cholesterol, look up your MYRF gene. rs174537. T is the slow allele which leads to lower cholesterol/ I finally have a good one on this (T,T) but I am afraid it leads to my nerve damage.
Why do you believe that rs174537 causes nerve damage? Why do you believe that you have nerve damage? Has a doctor diagnosed this in you?

Approximately 30.3% of the world population has a T allele on that SNP. Is it your personal belief that 2.2 billion people have nerve damage or are at risk of it due to this SNP?
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
Interestingly, Yasko calls out the rs4646406 snp and refers to it as a “2nd Priority” snp, one that ought to be addressed. I am homozygous AA, according to 23andme, the “Risk” allele. But Promethease lists me as TT, and its favorability is “Not Listed.” Can you clarify what appear to be common discrepancies of these two reports? I think I missed something in genetics 101!
Does this explanation help?
http://forums.phoenixrising.me/inde...ts-re-23-and-stirling-help.30156/#post-461213
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
A and T are sinonymous
C and G are sinonymous
The allele pairing with A is T
The allele pairing with C is G

No, they're called complementary.
Terminology wouldn't matter except that a synonomous snp is already a term used to mean something different.

A synonomous snp is one where a change in the allele doesn't result in a change to the protein produced by the gene. There are several different sets of instructions which lead to the same protein. (As opposed to a missense snp where the change does lead to a different protein for example)
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
SUOX rs10876864
GG

@ahmo....THIS is great.

SUOX (Sulfite Oxidase) is responsible for turning Sulfite into sulfate. When people have this SNP they will be sulfite sensitive if they are low in the cofactor for the gene, Molybdenum.

You are homozygous for this and it definitely will slow down your your conversion and make you sensitive. I am AG for this and I WAS sulfite sensitive until I took Molybdenum for a while. This is one of the genes I look and people are amazed at the clarity they have when they take Molyebdenum for the first time to treat this SNP.

Since this is a metal it will take a while to get out of the body so I started with a dose of 500mcg for a few days and stopped. Now, if I feel brain for or any other sulfite sensitivity I take more. But I also eat buckwheat which can be high in Molybdenum.

Two things clued me in that you old have this polymorphism; the fact that you had brain fog and your reaction to eggs. In fact I think any cysteine (sulfur) you take or eat will cause you issues until you supplement with Molybedenum.

I feel this is a greatly under appreciated SNP with people who have health issues. And everyone I have the genetics for who say they have "brain fog" have this SNP. I also tend to see this always in Autistics (note that I am not saying it causes Autism).

Sulfate is hugely important but if you have this SNP and are deficent in Molybdenum you will not make as much sulfate but you will suffer from too many sulfites.

http://physrev.physiology.org/content/81/4/1499
All cells require inorganic sulfate for normal function. Sulfate is among the most important macronutrients in cells and is the fourth most abundant anion in human plasma (300 μM). Sulfate is the major sulfur source in many organisms, and because it is a hydrophilic anion that cannot passively cross the lipid bilayer of cell membranes, all cells require a mechanism for sulfate influx and efflux to ensure an optimal supply of sulfate in the body. The class of proteins involved in moving sulfate into or out of cells is called sulfate transporters.

You might want to start a new thread on this!