Beyond MTHFR, other folate-related SNPs

[PeterPositive]

Hi,
I have the C677T homozygous mutation.
While trying to make sense of low serum and red blood cell THF, even with continuous supplementation, I went back to my 23andMe results and identified the following homozygous SNPs:

MTHFS
causes higher activity and folate depletion:
http://www.genecards.org/cgi-bin/carddisp.pl?gene=MTHFS&search=MTHFS

SLC19A1
reduced activity of folate transport proteins
http://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC19A1&search=SLC19A1

TCN2
diminished capacity of B12 transport to the cells
http://www.genecards.org/cgi-bin/carddisp.pl?gene=TCN2&search=TCN2

I don't see these mutations cited very often and I was wondering if they should be taken into consideration or not.

At the end of the day what counts is the actual state of active folate more than these SNPs, but I was trying to find possible causes for the problem.

cheers

 

[Critterina]

Peter,
There's a thread on here about MTHFS and we were trying to figure out whether it causes folinic acid intolerance (assuming I remember correctly). I too am homozygous for it. I took folinic acid and it made me very sleepy to begin with, but then I was OK with it. After that I seemed to tolerate it, but I no longer use it, now that I've thought through the equilibriums associated with my heterozygous MTHFR A1298C. But since you're homozygous MTHFR C677T, you wouldn't be considering folinic acid anyway.
Experientially, I sometimes throughout my life have had sharp instantaneous pricks, usually in my feet or legs, that I call "ghost needles" for lack of a better word. Just plain old folic acid supplementation fixes them, so even with my MTHFS, enough of it was getting through. FWIW.
Crit

 

[PeterPositive]

Peter,
There's a thread on here about MTHFS and we were trying to figure out whether it causes folinic acid intolerance (assuming I remember correctly). I too am homozygous for it. I took folinic acid and it made me very sleepy to begin with, but then I was OK with it. After that I seemed to tolerate it, but I no longer use it, now that I've thought through the equilibriums associated with my heterozygous MTHFR A1298C. But since you're homozygous MTHFR C677T, you wouldn't be considering folinic acid anyway.
Experientially, I sometimes throughout my life have had sharp instantaneous pricks, usually in my feet or legs, that I call "ghost needles" for lack of a better word. Just plain old folic acid supplementation fixes them, so even with my MTHFS, enough of it was getting through. FWIW.
Crit

Interesting. I take a small dose folinic acid in my B complex (~200mcg). I can't feel any difference, neither in the short nor in the long run.

Even with that plus daily consumption of salads the levels of folinic acid in my methylation panel are insufficient
So I don't event think I could theorize that folinic acid is competing with THF. There isn't enough of both to even talk to each other, much less compete

The only form I've got plenty of is good old folic acid, which I have stopped taking around Nov. 2013 but I still got a truckload in my serum, and I can't use it!

 

[Helen]

@Peter,

Could you have an infection (or any other stressor as toxins) that put demand on your methylation? I couldn´t raise my level of folates though supplementation and later I was diagnosed with Lyme. Your enzyme activity beeing homozygote for MTHFR C677T is low without supplementation as you know. Do you need even more folates? Interesting thread.

 

[PeterPositive]

@Peter,

Could you have an infection (or any other stressor as toxins) that put demand on your methylation? I couldn´t raise my level of folates though supplementation and later I was diagnosed with Lyme. Your enzyme activity beeing homozygote for MTHFR C677T is low without supplementation as you know. Do you need even more folates? Interesting thread.

That's a very good point.
It's the egg and chicken problem as far as I know. Is low methylation cause or effect? Could even be both Ah... if things were only true or false... Life would be easier and probably very boring too, I suppose... lol.

I have a problem with blastocystis hominis in my GI system which may be indeed overtaxing my methylation.

As regards Lyme, I never tested. I live in northern Italy, it doesn't seem very prevalent here. Also I don't live in the country and don't have pets. Wouldn't you know if you have been bitten?

cheers

 

[Critterina]

ISo I don't event think I could theorize that folinic acid is competing with THF. There isn't enough of both to even talk to each other, much less compete.

That's an interesting way to think of it, but, yes they do talk to each other. I think of it this way:

Folinic acid gets turned to methylfolate by the MTHFR enzyme, but it's a reversible reaction, so methylfolate also gets turned to folinic acid by the MTHFR enzyme. The two try to exist in equilibrium, as in most reversible reactions, so on the whole, adding more of one makes more of the other, until they are in balance (ignoring for the moment that both of them can be part of other reactions). If this were the end of the story, all would be well.

However, the process of achieving equilibrium is affected by the SNPs. The "forward reaction" (folinic acid to methylfolate) gets affected (slowed down) by the C677T mutation. The "backward reaction" (methylfolate to folinic acid) gets affected (also slowed down) by the A1298C reaction.

In this case, both SNPs slow down the reaction. But others, like the MTR A2756G in my signature, speed up the reaction.

Peter, you are smart and probably understand this already, but I thought I'd put it out there anyway. The main point is that the tiny bit of folinic acid doesn't seem to affect you, so no problem. Too bad about your boatload of folic acid!

Crit

 

[Critterina]

As regards Lyme, I never tested. I live in northern Italy, it doesn't seem very prevalent here. Also I don't live in the country and don't have pets. Wouldn't you know if you have been bitten?

Unfortunately, no. A member of my family contracted Lyme's in Texas, when there was not yet any record of any Lyme disease there. (And so she went misdiagnosed for many years.) She had no memory of a bite.

 

[PeterPositive]

Unfortunately, no. A member of my family contracted Lyme's in Texas, when there was not yet any record of any Lyme disease there. (And so she went misdiagnosed for many years.) She had no memory of a bite.

Ouch, I see.
Well then, I guess it wouldn't hurt to get tested.

Thanks

 

[roxie60]

@PeterPositive you would not likely feel a tick bite, their saliva numbs the area they bite. You might feel them moving before attaching but many never feel the bite, see the tick or rash.

 

[PeterPositive]

@PeterPositive you would not likely feel a tick bite, their saliva numbs the area they bite. You might feel them moving before attaching but many never feel the bite, see the tick or rash.

Thank you. I really know very little about this. I was under the impression that you would get redness and swelling based on some pictures of tick bites I've seen in the past.

Since I am going to have a few more tests done in the near future, I will add this one as well.

Cheers

 

[Helen]

That's a very good point.
It's the egg and chicken problem as far as I know. Is low methylation cause or effect? Could even be both Ah... if things were only true or false... Life would be easier and probably very boring too, I suppose... lol.

I have a problem with blastocystis hominis in my GI system which may be indeed overtaxing my methylation.

As regards Lyme, I never tested. I live in northern Italy, it doesn't seem very prevalent here. Also I don't live in the country and don't have pets. Wouldn't you know if you have been bitten?

cheers

Agree about egg and chicken ...I am curious too about the answer to your question - low methylation , cause or effect. Time will tell, but so far there is no research of this as far as I know.

Also the medications for Blastocystis hominis might be troublesome with certain enzyme defects in the detox system as far as I could see.

I live in an area with many infected ticks and it is common that people have been infected with Lyme without any symptom or sign of a tickbite. There are also claims that you can get infected in other ways than from a tick. Good idea to get tested as for all people with ME or CFS. Maybe the infected ticks have crossed the border to northern Italy.... They are numerous in neighbour countries according to research. / Best

 

[Valentijn]

As regards Lyme, I never tested. I live in northern Italy, it doesn't seem very prevalent here. Also I don't live in the country and don't have pets. Wouldn't you know if you have been bitten?

I was bitten dozens of times, maybe hundreds, and never once felt anything. The only way to detect them is visually, but they drop off after they get their fill, and some are very small as well. Hence it would be pretty easy to miss one, especially if it found a nice safe crevice to hide out in

One thing we didn't know 20 years ago when living in tick country was that they do drop off on their own. We knew we were safe if we got them off fast enough, but thought they stayed attached indefinitely until we removed them. So we probably missed some that way while thinking we were being quite safe.