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Which test shows the PEMT SNP?

Messages
15,786
You can look it up in your 23andMe data this gene or SNP: PEMT rs4646406

AA is the bad one. Tomorrow I will start some choline supplementation exactly with this purpose.
Is there research somewhere showing that it causes problems? All I can find are a couple abstracts (full text costs money), which says it has an association with a couple other SNPs, but no mention that it alters functionality of PEMT or that choline is helpful.

It's not a missense mutation, and AA is present in about 31% of Europeans.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Hi,
Recently I have started taking Choline and noticed great improvement.
@Peyt,
I have to ask: Improvement in what???
Reading along this thread, I checked out the three SNPs, and I'm hetero (+/-) for all three.
PEMT rs4244593 T GT
PEMT rs4646406 A AT
PEMT rs7946 C CT
Before I pour myself into researching these, I sort of want to know what the potential payoff is, as you see it. Thanks!
 

Peyt

Senior Member
Messages
678
Location
Southern California
Before I tell you the benefits I want to say that I don't think you will benefit as much as me, simply because I don't see COMT++ in your list of SNPs,
but here is the benefits I have been experiencing:
1. Less headaches by 70%
2. Less upper body stiffness by 30%
3. Less anger and agitation by 70%
4. I smile and laugh more
5. I feel a bit more focused 20%

I actually decided to start Choline after reading an old info page written by Dr. William Walsh from back in 2003 about Overmethylated people with ADHD.... I don't think you are an over-methylater because I don't see COMT++ in your SNPs. Besides, it says in your signature that you are Histamine intolerant which is the opposite of an overmethylator, if anything, by Dr. Walsh's terminology you would be an undermethylator although you would have to be tested to find out for sure.... .I have a feeling if someone has COMT++ and PEMT + together then taking Choline will help alot like it is doing for me... .. My reason is because the person with COMT++ will have excess Dopamine and Neropenephrine and if he/she has PEMT then there is deficiency in acytocoline.

Well Dopamine, Epinephrine and acytocoline are all important brain neurotransmitters...IMO, if there is excess in one or two and deficiency in another, it can causes a greater imbalance then if there is just deficiency in Choline but the other 2 are normal.

Here is the page on Dopamine, Choline and ADHD by Dr. Walsh from 2003... this man in brilliant:
http://www.alternativementalhealth.com/articles/walsh.htm#AD
 
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Peyt

Senior Member
Messages
678
Location
Southern California
Just wanted to give an update,
After using Choline for 2 weeks some of the benefits I was feeling before have diapeared, but here is what I am still benefiting by using 500mg of Choline B.

1. I have not had a headache in the last week
2. I still feel less upper body stiffness
3. I feel less bloating and gas, I have heard that Choline can help bile flow which I have always had a problem with so
I wonder if this is why I feel less bloated after eating.
4. I have lost 3 Lbs in 2 weeks. which was surprising since I have not changed my diet

But the feeling of agitation and anger was back today, so I took some of the other Choline (phosphatidylcholine) and I feel calmer and less agitated... the problem with Phosphatidylcholine is I usually gain weight .... who knows maybe the 2 will cancel eachother out...

Realizing how much difference there is between Phosphatidylcholine and Choline bitartrate makes me curious to order the Choline Ahmo posted earlier to see if there is other benefits... All I can say is Choline (of some sort) is a keeper for me at this point,
 
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Peyt

Senior Member
Messages
678
Location
Southern California
Update (I am learning as I go)
after running my genetic genome on nutrahacker i learned there is another gene besides PEMT that effects Choline and that is MTHFD1
So mutation of MTHFD1 requires Choline while mutation of PEMT requires Phosphatidylcholine
Unfortunately, I am +/- on both!
 

aquariusgirl

Senior Member
Messages
1,732
Ok, I've been trying to investigate my PEMT status. PEMT has an impact on fatty liver, bile, mito membrane fluidity, schizophrenia etc.

Estrogen is involved with regulating with PEMT, so there's an X factor here.

So it came to my attention that some women who did the Patricia Kane protocol...IVs of PhosCHol ...said it gave them their "brains back."

Incidentally, I accidentally discovered I had fatty liver during an ultrasound to investigate gallbladder problems a couple of years ago.

I just ran a PEMT template on Livewello & the genes are either green or red...and there's a lot of red....
I guess the literature flags these 3 ...but my 23andme chip doesn't have the last one & I am ok for the first 2.

PEMT rs4244593 GG
PEMT rs4646406 AA
PEMT rs7946 No call

But on Enlis, all my PEMT variations are on INTRONs .....65 DNA variations ...all on Introns... which stacked against the other genomes I have is unusual.

So I'm wondering if estrogen is off, would that affect PEMT expression?


Thanks
 

alicec

Senior Member
Messages
1,572
Location
Australia
So I'm wondering if estrogen is off, would that affect PEMT expression?

There is an oestrogen response element in the promoter of PEMT, so oestrogen can increase production of this enzyme.

The result is that premenopausal women are protected from the deleterious effects of a low choline diet, compared with men and post-menopausal women.

Note that if dietary choline is adequate, oestrogen gives no particular advantage where PEMT is concerned.

As for PEMT SNPs, as far as I am aware, of the three you list, only rs7946 has been characterised as affecting PEMT activity. The change to the protein does reduce activity of the enzyme though the effect does not seem to be dramatic. There is an increased risk of developing NAFLD, but having the SNP doesn't necessarily mean that this will occur.

The other two SNPs you list I think appeared in small association studies which may or may not mean anything.

As for the Livewello templates, these are just lists of SNPs that people have put together - they don't necessarily mean anything and in the case of PEMT, apparently they don't.

On the oestrogen response of PEMT, a relatively recent study has identified two SNPs in linkage disequilibrium which affect the capacity of oestrogen to regulate PEMT.

rs12325817, in the promoter region of the gene near the oestrogen response element, appears to have the actual effect. The presence of the variant C allele interferes with oestrogen binding to the response element and hence abrogates the protective effect of oestrogen for pre-menopausal women.

Post menopausal women with this SNP are more susceptible to choline deficiency, but as might be expected, men are not affected.

Other genes affect susceptibility to choline deficiency. Here is a paper looking at relevant SNPs. Again note that the effects are relevant in face of inadequate dietary choline. If this is sufficient, the SNPs are not relevant (to choline metabolism at least - they might have other significance).

ETA Here is another study from a slightly different angle, looking at the effect of SNPs in folate-related pathways which increase need for choline.
 

aquariusgirl

Senior Member
Messages
1,732
Can anyone explain this.. Livewello says neither my mom or I have the variant allele for MTHFD1 1950902. we're both GG

but Enlis says I have 2 DNA variations..

and under the mRNA box, it shows we both have missense x2 for this variant. A/G

I googled missense...but I still don't get it. Help[!
 

alicec

Senior Member
Messages
1,572
Location
Australia
Can anyone explain this.. Livewello says neither my mom or I have the variant allele for MTHFD1 1950902. we're both GG

but Enlis says I have 2 DNA variations..

and under the mRNA box, it shows we both have missense x2 for this variant. A/G

I googled missense...but I still don't get it. Help[!

Missense just means that a nucleotide change results in a change to the protein product of the gene.

I'm not familiar with the detail of how Enlis reports thing but I think this is saying that you have a homozygous variant (ie 2 x means on both strands) which results in a changed protein product (missense). A/G is just showing the alternative alleles at the SNP position.

By contrast Livewello is saying you don't have the variant allele.

So the question is what is the wildtype or major allele and what is the variant allele and what is causing the confusion.

If you look at the dbSNP entry under MAF (minor allele frequency) you will see that the minor allele is A, reported on the genome orientation - in other words, you are homozygous for the major allele (G).

But just above this is says that the ancestral allele is T and further that the alleles are reported in reverse orientation to the genome (the database is just recording information the way it was deposited). So you need to reverse this T to get the ancestral allele in the same orientation as the genome - which brings you back to C/G as the ancestral allele - the version that you have.

This is the source of confusion, but really Enlis should be alert to this and be able to sort this out and report correctly.

If you look at the literature you can double check on these reversals to make sure you have got things the right way around.

In this paper for example you can see that the description of rs1950902 is C401T; R134K - in other words the nucleotide change is from C to T (ie T is the variant allele) with the resultant protein change of arginine to lysine (R > K).

So Livewello is correct.

In any case, even if you did have the variant, dbSNP reports it as benign.