Genetic variants (SNPs) Interpretation Guide

[caledonia]

Yes, that happened to me. I was doing a betaine test to see how much I needed and once I got to 4 pills/meal I went off the charts. I didn't sleep for 3 days, went back into psychosis and was in overall really bad shape.

I'm not saying everyone will have those crazy reactions but those are what I deal with regularly, they were just severely increased with too much Betaine HCL

I was taking 2 pills per meal. Maybe that was the difference. Beyond 2 pills I had a burning sensation so I didn't try to go any higher.

 

[dannybex]

Yes, that happened to me. I was doing a betaine test to see how much I needed and once I got to 4 pills/meal I went off the charts. I didn't sleep for 3 days, went back into psychosis and was in overall really bad shape.

I'm not saying everyone will have those crazy reactions but those are what I deal with regularly, they were just severely increased with too much Betaine HCL

Interesting. That's quite a strong reaction, especially not sleeping for three days. I think that would make anyone somewhat psychotic. Hope you're doing better.

I've definitely been overstimulated, but have been that way for even a few years before I crashed in 1998. And didn't start taking betaine HCL until 1999 or so. I had a temporary remission from late 99 to very early 2001, so not sure if the betaine is an issue, but will try to cut back and see if my gastroparesis/poor digestion gets any worse.

 

[dannybex]

I was taking 2 pills per meal. Maybe that was the difference. Beyond 2 pills I had a burning sensation so I didn't try to go any higher.

Someone told me in an email to drink more water w/the betaine HCL and wait 5-10 minutes before eating. I've done that the last couple of meals, and it seems to help lower the dose. Makes sense as how can the acid really be created if there isn't enough liquid in the stomach? I was hardly drinking anything w/meals...

 

[Aerose91]

Interesting. That's quite a strong reaction, especially not sleeping for three days. I think that would make anyone somewhat psychotic. Hope you're doing better.

I've definitely been overstimulated, but have been that way for even a few years before I crashed in 1998. And didn't start taking betaine HCL until 1999 or so. I had a temporary remission from late 99 to very early 2001, so not sure if the betaine is an issue, but will try to cut back and see if my gastroparesis/poor digestion gets any worse.

Psychosis has been one of my main symptoms in this since the beginning so taking the HCL only emphasized it.

I was trying what @caledonia mentioned and seeing what my tolerance was until I got burning. At 5 pills/meal I still didn't have burning but it effected my brain function so much I had to stop.

 

[Aerose91]

Someone told me in an email to drink more water w/the betaine HCL and wait 5-10 minutes before eating. I've done that the last couple of meals, and it seems to help lower the dose. Makes sense as how can the acid really be created if there isn't enough liquid in the stomach? I was hardly drinking anything w/meals...

Funny, when I was treating my adrenal fatigue (before I had ME) they said not to drink before eating because it dilutes your digestive juices. I'm not saying either is right or wrong, just noticing how there's many differing opinions out there.

 

[dannybex]

Funny, when I was treating my adrenal fatigue (before I had ME) they said not to drink before eating because it dilutes your digestive juices. I'm not saying either is right or wrong, just noticing how there's many differing opinions out there.

Same here. That's why I cut way back on water w/meals. But again, two more meals later, drinking about 1/3rd to 1/2 cup of water w/the betaine HCL, and then waiting about five minutes before eating, has allowed me to cut the number of capsules from seven down to four. Will see if I can go lower.

 

[Aerose91]

Same here. That's why I cut way back on water w/meals. But again, two more meals later, drinking about 1/3rd to 1/2 cup of water w/the betaine HCL, and then waiting about five minutes before eating, has allowed me to cut the number of capsules from seven down to four. Will see if I can go lower.

I'm going to give that a try, see if it helps. Thanks for the suggestion.

 

[veganmua]

@caledonia I can't open the SNPs Interpretation guide! It just comes up as a blank page in my browser!

 

[dannybex]

@Critterina

So what's your position on folinic acid? I'm glad you've picked up on it, I'm just so impressed w/ the guide, haven't reviewed it forensically. (I'm pretty much incapable of reviewing anything forensically!)

I ask because I found folinic did nothing for me, tho I tried it several times. I eventually found that vegetable folate, ie. folinic, in fact blocks Mfolate for me. I had to eliminate my green veg to bring down my Mfolate dose from 25mg to 15mg.

I thought that B2 (riboflavin) required to convert folinic into methylfolate?

You've probably answered this elsewhere, but I'm curious what specific reaction or reactions did you have to folinic?

I feel it helps me calm down and sleep better, although not to the point of narcolepsy like @Critterina …

p.s. Here's a case study where folinic and riboflavin were used to help a young boy with mitochondrial complex I encephalomyopathy, suggesting that it helped raise his 5MTHF levels(?) :

http://orbi.ulg.ac.be/bitstream/226...bral 5- methyltetrahydrofolate deficiency.pdf

 

[ahmo]

@dannybex At the time I tried folinic and found no help I was also using high doses of Bs, most likely including B2. This was in my trials of the SMP, before I switched to Freddd's Protocol. More recently, I'd been reading the B2 thread and a reference to folinic. I took it for about 3 days, and found that I could eat some lettuce on those days w/o going into the adrenal overload that greens had precipitated in the past. However by Day 3, I was swamped by ammonia, it seemed. It took me some days to eliminate it from my system. I'd love to eat green veg, but won't be trying again in the near future.

My original understanding re folinic and methylfolate came last year, when I'd been raising my Mfolate higher and higher, following deficiency symptoms, until I was showing significant adrenal symptoms in my face, and moving on to low back. I'd been up to 25mg Mfolate. I stopped eating the 2 zucchinis I'd been eating most days, and my ongoing detox process went into overdrive, such that I could barely manage it. Removing the folinic unblocked the folate. I stopped all folate for nearly a week, and when I resumed it, dropped from 25 to 15mg. That's since been reduced to 5mg by switching to putting it in my gum, instead of swallowing.

 

[dannybex]

Thanks @ahmo. I don't quite understand the ammonia connection though. From vegetables?

 

[ahmo]

@dannybex I don't know if I'm able to correctly differentiate ammonia from sulfur issues. I've been spending hours trying to understand this. I call it ammonia because using ammonia-reducing supps helps. Following the B2 episode, I suffered very similar symptoms from what was quite clearly oxidative stress, from prolonged excess activity. I'm working on understanding Martin Pall's NO/ONOO- info. I've just added a few of the things he suggests for lowering peroxynitrite, and have felt better. So, I'm unclear what the source of my high ammonia/sulfur is at present, as I eat no sulfur/high thiol foods. I've returned to some baseline after the high stress period. And am still needing lot's of supps to deal with the symptoms: weird taste in mouth, on the edge of agitation, slightly headachey, squinty-eyed, just 'not-right'. The next rabbit I'm chasing down this hole is candida, which contributes to high ammonia environment. Am ready to start an intensive protocol

 

[miss1521]

@caledonia

I was reading through your SNPs Interpretation Guide and I had a question. I am new to this stuff and still have so much to learn and research but thank you for posting the guide. Regarding First Priority Mutations: I am normal for ACAT, SHMT, and CBS C699T. For CBS A360A I am +/- Heterozygous. It says BHMT mutations will add to CBS problems and can even cause problems in the absence of SNPs. I am +/- Heterozygous for BHMT-02 and BHMT-04. Does this mean I could possibly still have CBS problems with only CBS A360A as Heterozygous? As for CBS expression, I'm not sure if I tolerate sulfur foods or supplements or not. As for methyl supplements, nutrahacker says I do not tolerate methyl donors. Although Magnesium Glycinate is not a methyl donor, it activates the NMDA gene (so I've been told) and causes problems for some people. I had a very serious reaction to Mag Glycinate including severe head pressure, swollen throat, neck, head, and insomnia. It wasn't serious enough for hospitalization but I think only because I had started small (120mg dose). With this in mind... should I be treating the CBS mutations as suggested in the list of First Priority Mutations?

Genetic Genie Results
Methylation Analysis Results:
VDR Taq +/+
COMT V158M +/-
COMT H62H +/-
MAO A R297R +/-
MTRR R415T +/-
BHMT-02 +/-
BHMT-04 +/-
CBS A360A +/-

Detox Profile Results:
CYP1B1 L432V +/+
CYP1B1 R48G +/+
NAT2 K268R +/+
CYP1A2 164A>C +/-
CYP2E1*1B 9896C>G +/-
CYP3A4*3 M445T +/-
NAT2 I114T +/-
GSTT1 Present

I read somewhere that COMT +/- and VDR +/+ together behave like COMT -/-. I don't know which COMT or which VDR that is talking about.

Any help would be greatly appreciated. I have another mutation that is never listed in any of the methylation or detox lists but is a very concerning one. I am wondering if methylation and detox need to be addressed before trying to address that one, which is SLC39A2 (mediates zinc uptake).

 

[jimsmth]

Quoting from your PDF:

Let’s start with C677T.

A normal un-‐mutated gene is called C677C. This means at the 677th position on the gene, there are two cytosines.

A mutated gene is called C677T. Notice that one of the cytosines has been replaced with a thymine. This one small change is enough to impair it’s functioning.

Caledonia

That description does not seem to be correct. I'm new to this, but the SNP nomeclature works like this:

C677T means that the "normal" (also called "wild type") nucleotide base at that position is C and the change is to a T. So T has replaced the normal C. It's a single change.

A single non-mutated gene would not have two C's at that position. It would have one. And a mutated gene would not have a C and a T, it would have only one T that has replaced the C.

We do have two copies of each gene. But each copy of the gene will only have a single change for a SNP. That's by definition because it is a single nucleotide polymorphism.

The idea of one vs. two mutations comes in with the heterozygous (one change) or homozygous (two changes) as denoted by the -/+ or +/+ symbols.

If you are +/+ for C677T, each of the two copies of the MTHFR gene will have a single T where there was a single C (at position 677). You have two SNPs in that case and you are homozygous for this SNP.

Please correct any mistakes I've made.

 

[Valentijn]

It's also probably at position 665 according to most sources, not 677. C677T is just the more traditional name, but probably not accurate. Protein positions (A222V in this case) are more reliable and descriptive, which is why I generally prefer them, but some SNPs have already become too well-known using their inaccurate gene positions.

 

[caledonia]

Quoting from your PDF:


That description does not seem to be correct. I'm new to this, but the SNP nomeclature works like this:

C677T means that the "normal" (also called "wild type") nucleotide base at that position is C and the change is to a T. So T has replaced the normal C. It's a single change.

A single non-mutated gene would not have two C's at that position. It would have one. And a mutated gene would not have a C and a T, it would have only one T that has replaced the C.

We do have two copies of each gene. But each copy of the gene will only have a single change for a SNP. That's by definition because it is a single nucleotide polymorphism.

The idea of one vs. two mutations comes in with the heterozygous (one change) or homozygous (two changes) as denoted by the -/+ or +/+ symbols.

If you are +/+ for C677T, each of the two copies of the MTHFR gene will have a single T where there was a single C (at position 677). You have two SNPs in that case and you are homozygous for this SNP.

Please correct any mistakes I've made.

I did a quick google search. It appears that saying either C677T or 677T would be correct.

For example, you can see C677C and C677T being used in this study: http://www.ncbi.nlm.nih.gov/pubmed/15004488

While 677T is used in this study. http://www.ncbi.nlm.nih.gov/pubmed/16522920

Now that I think about it, I believe I had just picked the most common naming scheme (or at least the one used by Yasko, Heartfixer, MTHFRsupport, etc.) just to keep things simple for beginners.

You can also use rs numbers.

 

[pogoman]

I think the MTHFR C677T defect and disease connection was one of the first to be discovered (I want to say around 1995) and may predate the current naming conventions?
But its snp is rs1801133 and this shows the various names for it.
http://www.snpedia.com/index.php/Rs1801133

 

[daisy mae]

Caledonia,
Thanks so much for the Nutreval Interpretation Guide. My daughter took that test so the guide is helpful in interpretating her results. My question is : Do you know the difference in the Nutreval test and the test that Yasko recommends---the MAP or OAT, the UEE and UTM, and UAA. Its all so confusing and I am knew at this. Thanks so much for your help.
Daisy Mae

 

[caledonia]

Caledonia,
Thanks so much for the Nutreval Interpretation Guide. My daughter took that test so the guide is helpful in interpretating her results. My question is : Do you know the difference in the Nutreval test and the test that Yasko recommends---the MAP or OAT, the UEE and UTM, and UAA. Its all so confusing and I am knew at this. Thanks so much for your help.
Daisy Mae

Hi Daisy Mae, I believe MAP, OAT and UAA measuements are incorporated, but it's not the same tests that Yasko uses. These are cheaper versions of similar tests. UEE and UTM (urine essential elements and urine toxic metals) are separate tests. Yasko uses Doctors Data. I have taken those and found them helpful for supplementation and treatment. If hits for mercury and lead are showing up on your Nutreval, you may want to take them.

 

[bertiedog]

Based on our experiences here on the forum, folinic is tolerated by some people, but not others. So if it's working for you, take it. If not, avoid it. As the reason for this is unknown*, the only way to know is to cautiously trial it and observe how your body reacts.

There is folinic acid in the 3 Thorne Basic Nutrients I have been taking since 2007 (thanks to the much missed Rich Vank) and I don't have any problems with it all whereas when I add say 400 mcg methylfolate that is another matter. I cannot tolerate that amount extra despite me having many SNPs which mention problems with folate transport.

This is serious for me because the problem is so severe for me that I had a still born baby with a neural tube defect in 1973 and in the recent Livewello report, neural tube defects come up all over the place because of the problem with folate. I do not however have the famous MTHFR 677T but one copy of the minor MTHFR 1298.

Whenever I add in more methylfolate I am in troubling with unremitting migraines so I am going back to basics having reread @caledonia's great resource and reading Heartfixer's comments on CBS + + and BHMT + +. I am going to try and add all my SnPs to my signature when I get round to it!

I do eat a lot of folate each day but the last Organic Acid test I had seemed to show I needed more and after going through all my SNps showing up in the recent Livewello report I think I can see why.

Pam