Genetic variants (SNPs) Interpretation Guide

[Valentijn]

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!

Their claims about CBT and BHMT are baseless.

 

[bertiedog]

Their claims about CBT and BHMT are baseless.

You might well be right, I don't know but it won't hurt for me to test my sulphate levels anyway to give me some idea as to whether I have high sulphate and possibly ammonia too. I know in the past I seemed to notice a strong ammonia smell at times but I haven't noticed this recently.

Pam

 

[caledonia]

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!

Check out Ben Lynch's two articles on how to prevent methylfolate side effects. Migraines are on the list of side effects (as you have figured out already).

http://mthfr.net/methylfolate-side-effects/2012/03/01/

http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/

 

[bertiedog]

Their claims about CBT and BHMT are baseless.

Well I have some more information regarding CBS++ and not tolerating sulphur. This is definitely me. I did get the sulphate test strips through and tested around 800 which I think is ok.

On Wednesday I took one Reduced Glutathione at lunchtime and by the evening a wave of tiredness hit me with a sense of dizziness. I couldn't work on the jigsaw that I usually do for part of the evening, I had to lie down and felt horrible. The next day, soon after waking a migraine started and I used another test strip. This time it was a lot higher, probably over 1200 and I felt like crap.

Therefore I have to believe that indeed there is something in what Heartfixer and Yasco has said regarding CBS++ and maybe the BHMT too.

I have never been able to tolerate any glutathione even though when tested by Dr McClaren Howard it was lowish. However I am going to try a GSH patch and wear it for a few hours as suggested and see if I can tolerate that. The reason I am keen to raise this is because I have had heavy metal poisoning in the past (mercury and nickel) and know that I don't detox it properly, again probably because of my dodgy genetics.

Pam

 

[Valentijn]

Therefore I have to believe that indeed there is something in what Heartfixer and Yasco has said regarding CBS++ and maybe the BHMT too.

Most people are CBS++ for some SNPs. They are extremely common. Hence it is expected that many people will react to various things, without that reaction having anything to do with CBS.

 

[bertiedog]

Most people are CBS++ for some SNPs. They are extremely common. Hence it is expected that many people will react to various things, without that reaction having anything to do with CBS.

Maybe so but they don't have the other SNPs that I have which presumably interact and can cause biochemical imbalances. My past Organic Acid tests confirm this.

Pam

 

[Valentijn]

Maybe so but they don't have the other SNPs that I have which presumably interact and can cause biochemical imbalances. My past Organic Acid tests confirm this.

And there's the problem. You're presuming (incorrectly) that those SNPs are 1) relevant and 2) part of a small group of SNPs which can be relevant. But they aren't relevant in the manner suggested. Some are shown to have no impact, others aren't studied, and some have a very mild beneficial impact which would not be noticeable.

The sensible conclusion is that something is happening for some other reason. A big old "we don't know." Not as satisfying as a simple system of this SNP doing X and that one doing Y and "fixing" it all with A, B, and C, but much more reflective of reality.

Yasko has created a system of easy answers. But the basis for it is completely flawed.

 

[bertiedog]

@Valentijn With respect that is your opinion, others might think otherwise.

Pam

 

[Valentijn]

@Valentijn With respect that is your opinion, others might think otherwise.

Perhaps. But I'm basing my opinion on the scientific research, logic, and rationality.

Their opinions are based on the selective reading of anecdotal reports, lack of understanding regarding basic scientific and statistical concepts, and often a complete distrust of science. Hence those resulting opinions are nearly always wrong.

 

[bertiedog]

So @Valentijn is it your theory that the much missed Rich Van Kronenburg, a retired biochemist who put together the Simplified Methylation Protocol which benefited many with ME/CFS didn't know what he was talking about regarding the various SNPs and the effects they had in the body? Because it rather sounds that way to me.

Pam

 

[Valentijn]

So @Valentijn is it your theory that the much missed Rich Van Kronenburg, a retired biochemist who put together the Simplified Methylation Protocol which benefited many with ME/CFS didn't know what he was talking about regarding the various SNPs and the effects they had in the body? Because it rather sounds that way to me.

He was interested in SNPs, but I don't recall him making claims about specific ones having effects which were contradicted or unsupported by science.

And in any event, it's quite possible to disagree with nice and intelligent people about theories.

 

[caledonia]

Well I have some more information regarding CBS++ and not tolerating sulphur. This is definitely me. I did get the sulphate test strips through and tested around 800 which I think is ok.

On Wednesday I took one Reduced Glutathione at lunchtime and by the evening a wave of tiredness hit me with a sense of dizziness. I couldn't work on the jigsaw that I usually do for part of the evening, I had to lie down and felt horrible. The next day, soon after waking a migraine started and I used another test strip. This time it was a lot higher, probably over 1200 and I felt like crap.

Therefore I have to believe that indeed there is something in what Heartfixer and Yasco has said regarding CBS++ and maybe the BHMT too.

I have never been able to tolerate any glutathione even though when tested by Dr McClaren Howard it was lowish. However I am going to try a GSH patch and wear it for a few hours as suggested and see if I can tolerate that. The reason I am keen to raise this is because I have had heavy metal poisoning in the past (mercury and nickel) and know that I don't detox it properly, again probably because of my dodgy genetics.

Pam

The glutathione patch probably isn't going to be any better than the supplement.

Mercury can make CBS express causing sulfur intolerance and also methyl group intolerance.

In the case of sulfur intolerance, Cutler suggests taking the two precursors of NAC (glutamine and glycine) instead of taking glutathione. NAC could also possibly work. NAC is a precursor of glutathione.

You can also do CBS treatment to get the transsulfuration pathway working correctly. Then do methylation treatment which will indirectly create glutathione.

However, if you have metals, the best way to get them out is via Cutler's frequent dose chelation protocol. If you only dose once a day instead of every few hours, you will end up redistributing the metals and feeling worse. I'm getting ready to embark on this myself.

It would be best to have the transsulfuration pathway and methylation working correctly (as well as the gut) prior to working on metal chelation.

 

[Marc_NL]

Perhaps. But I'm basing my opinion on the scientific research, logic, and rationality.

Are there other SNP's that, based on scientific research, do say something about what they are doing and how these issues can be fixed?
I don't have my 23andme results yet but I am interested in information about this.

 

[caledonia]

Are there other SNP's that, based on scientific research, do say something about what they are doing and how these issues can be fixed?
I don't have my 23andme results yet but I am interested in information about this.

I'm sorry, I don't quite understand your question?

 

[Marc_NL]

I'm sorry, I don't quite understand your question?

My question relates to this post:

And there's the problem. You're presuming (incorrectly) that those SNPs are 1) relevant and 2) part of a small group of SNPs which can be relevant. But they aren't relevant in the manner suggested. Some are shown to have no impact, others aren't studied, and some have a very mild beneficial impact which would not be noticeable.

The sensible conclusion is that something is happening for some other reason. A big old "we don't know." Not as satisfying as a simple system of this SNP doing X and that one doing Y and "fixing" it all with A, B, and C, but much more reflective of reality.

Yasko has created a system of easy answers. But the basis for it is completely flawed.

If I understand it correctly @Valentijn says that some claims about SNP's and what they say are not based on scientific research so I was asking her if other SNP's do have more scientific evidence and where I can find the information.
Maybe I didn't understand, I'm new to all this.

 

[Valentijn]

Are there other SNP's that, based on scientific research, do say something about what they are doing and how these issues can be fixed?
I don't have my 23andme results yet but I am interested in information about this.

There is actual scientific research showing which SNPs (usually missense mutations or nonsense mutations) have a significant impact. This is why it's especially baffling that Yasko and her followers prefer to make things up about random SNPs that don't have any impact

There often is a way to compensate for the impact of pathogenic mutations. One example is the recommendation that pregnant women take folate during pregnancy, since low folate is correlated with increased birth defects.

But even significant mutations are usually not pathogenic - that is, they don't really cause disease. MTHFR C677T and A1298C are good examples of this. Although they result in significant reduction in methylfolate production (ranging from about 10% to 65%), they're so common that a reduction of about 30% seems to be the norm. It doesn't cause widespread problems outside of pregnancy however, because people can pretty easily get sufficient methylfolate from vegetables.

 

[Valentijn]

If I understand it correctly @Valentijn says that some claims about SNP's and what they say are not based on scientific research so I was asking her if other SNP's do have more scientific evidence and where I can find the information.

One way to check is on dbSNP. Pathogenic mutations are clearly marked, with a link to the OMIM database of genetic disorders for that SNP. And non-pathogenic (or unknown status) SNPs are also marked as being missense mutations. The relevant research is also linked there, if there is any.

I'm trying to get a new version of the Analyze My Genes program ready for download, with rare (or all) missense mutations flagged, as well as their benign/pathogenic status marked when known. We've matched up the various relevant databases, but I still need to go through about 2000 results by hand where there are multiple results or a mismatch between alleles, etc, and sort them out.

 

[npeden]

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

bertiedog, i too am folate and sulfur sensitive again. i do not think it is leaky gut but it might be. i am homo for sod2 and that, according to that nasty nutrahacker, is responsible for folate metabolism. on lynch's site someone says sulfur but on my report the snp no. goes to a folate snp. anyway, in that nasty nutrahacker, i just noticed recommendation of mangenese for sod2. as it is a metal i believe it must be very low doses. my nd, who is pretty mature, agrees and says 3 mg. per day. i found some that comes in drops, so i hope i can get a low dose. sod2 is about oxidative stress which is all about redox signalling. that is what i am in here looking up. but if mangenese would allow me to eat green, that would be great. and i am looking into redox...

 

[npeden]

One way to check is on dbSNP. Pathogenic mutations are clearly marked, with a link to the OMIM database of genetic disorders for that SNP. And non-pathogenic (or unknown status) SNPs are also marked as being missense mutations. The relevant research is also linked there, if there is any.

I'm trying to get a new version of the Analyze My Genes program ready for download, with rare (or all) missense mutations flagged, as well as their benign/pathogenic status marked when known. We've matched up the various relevant databases, but I still need to go through about 2000 results by hand where there are multiple results or a mismatch between alleles, etc, and sort them out.

valentj, is there a way to get notices of updates?

 

[Valentijn]

valentj, is there a way to get notices of updates?

If you scroll down a bit at http://sourceforge.net/projects/analyzemygenes/ there's an option to fill in your email address under "KEEP ME UPDATED". Presumably that will automatically send an alert when there's new files or some other change ... though I've never used it' so can't say for sure.