Genetic variants (SNPs) Interpretation Guide

[caledonia]

Caledonia,
I see on your interpretation guide (detox profile section) you have a SNP called GSTT1. But I don't see that on my 23andme Detox Profile. Which test are you seeing this on? thanks

Found this post on the Genetic Genie Facebook which explains where it came from.
https://www.facebook.com/GeneticGenie/posts/671346229558594

MTHFR & Methylation analysis automation by geneticgenie.org
June 24, 2013 ·
Glutathione related genes (GSTT1 and GSTM1) were added to the detox profile to check for deletions. If you have the gene it is listed as present. If it is missing, it is listed as absent.

This is much different than a SNP as we are talking about the entire gene. 23andMe isn't technically designed to detect deletions, but I think this will work for most people.

If problems exist, let me know.

=-==-=-=
23andme has changed vchips since then, so it may no longer be tested for.

 

[Sea]

Found this post on the Genetic Genie Facebook which explains where it came from.
https://www.facebook.com/GeneticGenie/posts/671346229558594

MTHFR & Methylation analysis automation by geneticgenie.org
June 24, 2013 ·
Glutathione related genes (GSTT1 and GSTM1) were added to the detox profile to check for deletions. If you have the gene it is listed as present. If it is missing, it is listed as absent.

This is much different than a SNP as we are talking about the entire gene. 23andMe isn't technically designed to detect deletions, but I think this will work for most people.

If problems exist, let me know.

=-==-=-=
23andme has changed vchips since then, so it may no longer be tested for.

I think there can be partial deletions of the gene too, not just complete absence. We've discussed the GSTT1 deletion somewhere on here before. From memory there were 1 or 2 members with a "no call" for all 14 of the GSTT1 SNPs tested by 23andme, but there were also several, including me, with a "no call" for 12 out of the 14 SNPs.

 

[Peyt]

Found this post on the Genetic Genie Facebook which explains where it came from.
https://www.facebook.com/GeneticGenie/posts/671346229558594

MTHFR & Methylation analysis automation by geneticgenie.org
June 24, 2013 ·
Glutathione related genes (GSTT1 and GSTM1) were added to the detox profile to check for deletions. If you have the gene it is listed as present. If it is missing, it is listed as absent.

This is much different than a SNP as we are talking about the entire gene. 23andMe isn't technically designed to detect deletions, but I think this will work for most people.

If problems exist, let me know.

=-==-=-=
23andme has change
d vchips since then, so it may no longer be tested for.

Oh wow, so if GSTT1 is not on my Detox Profile report, I am missing a whole gene??
Nice..... lol

 

[Peyt]

Question on CYP1B1 on your guide.
It says for people with COMT or CBS (I am one of them) it's best to use Calcium d-‐glucarate
and I am very tempted to try this because I always felt I have poor estrogen metabolize, and
I may be wrong but I thought I read somewhere that Calcium is a Methyl Donor... now wouldn't a person with COMT want to stay away from Methyl Donors?
Thanks
Peyt

 

[npeden]

Thanks Caledonia for all your work!!

Double ditto. Lots of thanks.

 

[npeden]

Question on CYP1B1 on your guide.
It says for people with COMT or CBS (I am one of them) it's best to use Calcium d-‐glucarate
and I am very tempted to try this because I always felt I have poor estrogen metabolize, and
I may be wrong but I thought I read somewhere that Calcium is a Methyl Donor... now wouldn't a person with COMT want to stay away from Methyl Donors?
Thanks
Peyt

Peyt, I know it is not highly esteemed in some corners, but I really like nutrahacker.com's little 37 dollar report. It picks some clear snyps and hopefully the one's they choose do reveal which snyps are causing your methyl sensitivity.This is just from memory, but I think I have COMT and VDR as methyl sensitive.

Another cheap program that gives interesting reports is https://promethease.com/ondemandagreed It may be a little out of date, but it provides drug lists and diseases lists as compared to your 23&me report. It is a whopping 5 dollars.

Don't remember about calcium being a methyl donor. I can tolerate a little methyl.

BTW I have COMT and CBS and passionflower tincture, whose psycho active ingredient is harmaline, is doing wonders for my depression. This was my ND's rx for my treatment resistant depression. Also I am taking more and more hydroxy b12, up to 2400 mcg. daily now, hoping my depression and energy will get better.

Ok, I am sure I will be called out on being less than authoritative about methylation but I am MTHFR C677T and am getting to know my genes.

If any of you are interested, since this actually is not a MTHFR site, I invite you all to try the MTHFR community on google+. Dumb and brilliant questions and answers abound.

 

[Isa's Mom]

Hi All,

As there are more and more people coming on the forum asking for help with their SNPs, it's starting to get overwhelming. Therefore, I've prepared this guide to help people interpret their SNPs.

I'm asking for everyone's help to please bookmark this page and then refer people to this guide when they ask for help with their SNPs.

I will also put a link to this guide in my signature links, so you can also access it through any of my thousands of posts.

Caledonia

Hi, I'm new on the forum, although I've been doing research here for a while. I've been reading your SNP guide and I have a few questions I'm hoping you can answer.

Are the recommendations for certain polymorphisms, for example ACAT, the same whether we're hetero or homozygous?

I'm actually negative for ACAT, and have no info on SHMT because of the newer version of 23 and me, apparently. would it suffice to support SHMT with folinic acid or do the gut rebuilding program? I do not currently have gut issues, as I followed a strict diet several years ago to heal the gut and haven't had problems since. I've been gluten and dairy free a number of times and never noticed a difference.

I noticed a message someone posted about a place to post our genetic genie results but I haven't been able to find it. If anyone can point me in the right direction, I'd really appreciate it!

Cheers,

Aimee

 

[caledonia]

Hi, I'm new on the forum, although I've been doing research here for a while. I've been reading your SNP guide and I have a few questions I'm hoping you can answer.

Are the recommendations for certain polymorphisms, for example ACAT, the same whether we're hetero or homozygous?

I'm actually negative for ACAT, and have no info on SHMT because of the newer version of 23 and me, apparently. would it suffice to support SHMT with folinic acid or do the gut rebuilding program? I do not currently have gut issues, as I followed a strict diet several years ago to heal the gut and haven't had problems since. I've been gluten and dairy free a number of times and never noticed a difference.

I noticed a message someone posted about a place to post our genetic genie results but I haven't been able to find it. If anyone can point me in the right direction, I'd really appreciate it!

Cheers,

Aimee

Yes, whether you have one or two mutations (whether it's yellow or red), if you're having trouble in that area, you should provide support.

If your gut is ok, there's no need to do a gut program. Since we no longer know about SHMT, you can do a trial of folinic if you want to see if you tolerate it or not. But I think I would only do that if you were having gut problems.

Many multi supplements with methylfolate, such as the Thorne multivitamin, or Yasko's All in One multi have folinic in them, so you might end up taking folinic anyway.

In general, I think you're probably good to skip to CBS and see if treatment for that is required or not.

To post your SNPs, just make a new post in this subforum (Genetic Testing and SNPs).

 

[Isa's Mom]

Hi Caledonia,

Thanks a lot for your input!! This site is great as is your guide. It's a lot to get my head around in this state of ME/CFS, which I know goes for pretty much everyone on here! But I try to remember (was it dr yasko who said) "it's a marathon, not a sprint."

I read about CBS symptoms and I might be having them. It's hard to say. I feel lousy most of the time these days. Unfortunately, I can't get the sulfate test strips where I live (I have to order them from the States). Should I just jump to the no-sulfur diet or is it worth it to wait for the strips to arrive? I imagine it could take 2 to 3 weeks (unless someone knows of a source in Europe).

Also, has anyone made good progress with Rich's simplified methylation protocol? I was going to try that one, then realized that the metagenics b12 with intrinsic factor I have contains folic acid.

If I'm rambling and you'd like me to post on another forum (like methylation) just let me know!!!

Thanks a lot,

Aimee

 

[caledonia]

Hi Caledonia,

I read about CBS symptoms and I might be having them. It's hard to say. I feel lousy most of the time these days. Unfortunately, I can't get the sulfate test strips where I live (I have to order them from the States). Should I just jump to the no-sulfur diet or is it worth it to wait for the strips to arrive? I imagine it could take 2 to 3 weeks (unless someone knows of a source in Europe).

I guess that's your call. I didn't feel any different on the diet, but some people do. On the one hand, why go through a change of diet, if you don't have to. On the other hand, if your gut feeling is that you do have CBS issues, you might as well get started.

Also, has anyone made good progress with Rich's simplified methylation protocol? I was going to try that one, then realized that the metagenics b12 with intrinsic factor I have contains folic acid.

Rich's Simplified protocol is no longer current as Yasko has discontinued the Neurological Health Formula. You can substitute the All In One multi, but then drop all the other supps Rich suggested, except for a sublingual B12. If you don't drop them, you will be overlapping doses, as these other supps are now included in the new formula.

If you take a careful look at the ingredients, you'll see what I'm saying.

This is the core of what I'm doing and it's working well for me.

 

[Aerose91]

@caledonia

This is a huge help and answered a lot of questions I had, thank you.

I have to ask- what to you feel about Freddd's protocol? It seems that's the one to try now but it conflicts with a lot of things. He advocates methyl b12 only and other sources (yasko) say it may not be good. For myself if I take methyl b12 I get very revved up and tense- even while clearing sulphates. And wouldn't the amount of b12 you need be dependant on if you are +/+ or +/- for MTR? I wonder these things before continuing any further.

 

[caledonia]

@caledonia

This is a huge help and answered a lot of questions I had, thank you.

I have to ask- what to you feel about Freddd's protocol? It seems that's the one to try now but it conflicts with a lot of things. He advocates methyl b12 only and other sources (yasko) say it may not be good. For myself if I take methyl b12 I get very revved up and tense- even while clearing sulphates. And wouldn't the amount of b12 you need be dependant on if you are +/+ or +/- for MTR? I wonder these things before continuing any further.

I think it would work best for people with similar SNPs to Freddd. However, he hasn't gotten tested, so we don't know what those are. I would guess he doesn't have COMT, because he can tolerate high amounts of methylcobalamin.

There are many reasons to need B12, genetic as well as functional. But I think we could also guess that Freddd has the B12 double whammy, i.e. both MTR and MTRR mutations. I have links to a couple of good B12 articles in my signature below, which explain various reasons you could be low in B12.

 

[lyonsden10]

This is the clearest and easiest way I've found to understand specifics of my genotype issues. Thank you.

 

[Aerose91]

I think it would work best for people with similar SNPs to Freddd. However, he hasn't gotten tested, so we don't know what those are. I would guess he doesn't have COMT, because he can tolerate high amounts of methylcobalamin.

There are many reasons to need B12, genetic as well as functional. But I think we could also guess that Freddd has the B12 double whammy, i.e. both MTR and MTRR mutations. I have links to a couple of good B12 articles in my signature below, which explain various reasons you could be low in B12.

That was one of my biggest questions- the COMT thing. Since I've started mb12 I get super revved up which I'm assuming is COMT. Is there anything we can do directly to help COMT along? I haven't seen anything on it.

Do you agree with Freddd when he says mb12 is the only useful form? That hydroxy isn't very effective at all? According to the Yasko chart (thanks for that btw) I should be on hydroxy and adenb12, not methyl. However, if what I'm feeling is neurological healing I don't necessarily want to stop.

 

[caledonia]

That was one of my biggest questions- the COMT thing. Since I've started mb12 I get super revved up which I'm assuming is COMT. Is there anything we can do directly to help COMT along? I haven't seen anything on it.

Do you agree with Freddd when he says mb12 is the only useful form? That hydroxy isn't very effective at all? According to the Yasko chart (thanks for that btw) I should be on hydroxy and adenb12, not methyl. However, if what I'm feeling is neurological healing I don't necessarily want to stop.

There are people who do fine on hydroxy. When Freddd says mb12 is the only useful form, that actually means it's the only useful form for him and people with SNPs and functional issues similar to him. There is no such thing as a one size fits all protocol.

While there is a general procedure you can follow, everyone is an individual and will need to do somewhat different things according to their SNPs and/or functional issues. This is a new paradigm for medicine - Freddd is not approaching it from this angle. Which is not to say that there aren't things that can't be learned and borrowed from Freddd's protocol where useful (potassium deficiency on methylation startup being a hugely important discovery from Freddd).

I don't think there is really a direct treatment for COMT. The main thing is not to aggravate it with too many methyl groups. So either use hydroxy with or without adenosyl, or you might be able to get away with low doses of methylcobalamin. Some people might have COMT, but it isn't expressed, so they can take pretty good doses of methylcobalamin.

It could also be CBS. I was getting the classic stress/anxiety response from B12. I don't have COMT so that made it easier to figure out that it was CBS. I did the CBS protocol and now I can tolerate B12.

 

[PhoenixExperience]

Hi All,

As there are more and more people coming on the forum asking for help with their SNPs, it's starting to get overwhelming. Therefore, I've prepared this guide to help people interpret their SNPs.

I'm asking for everyone's help to please bookmark this page and then refer people to this guide when they ask for help with their SNPs.

I will also put a link to this guide in my signature links, so you can also access it through any of my thousands of posts.

Caledonia

Thank you so much - I find it very helpful!

 

[Aerose91]

Thanks @caledonia, I really appreciate the help

I wonder- is the reason methyl b12 isn't recommended for some is because it is just too uncomfortable? Because if that's the case I don't care about the discomfort- I just want what is most effective.

I have been working on clearing my CBS for a few weeks now and it is dropping. However I still get revved up even with 500 mcg methyl b12. It seems like my sulphates are always high first thing in the morning (around 1600) but then right back to normal range for the rest of the day. I can't figure out what's causing them to be high every morning.

 

[caledonia]

Thanks @caledonia, I really appreciate the help

I wonder- is the reason methyl b12 isn't recommended for some is because it is just too uncomfortable? Because if that's the case I don't care about the discomfort- I just want what is most effective.

MTHFRsupport says it causes more oxidative damage: http://www.mthfrsupport.com/mthfr-facts/

What kind of b12 should I be taking with my L-methylfolate and how much?

Your dosages should coincide with your b12 levels and many doctors that understand methylation are saying that the B9 (folate) and B12 ratio should be anywhere from 1:3 to 1:5. Methylcobalamin is the most active form of B12 and the one that most doctors that know about methylation and MTHFR prescribe but it is not a good idea for people with COMT V158M and H62H expressing. Individuals with these COMT genes usually need to do hydroxy and/or adenosyl B12. Methylcobalamin can do more oxidative damage to people with COMT expressing. Any doctors reading this will know when giving everyone methyl b12 that they have seen several come back with anxiety anywhere from two days to two weeks of being on high doses. COMT is where you should look at if that happens.

I have been working on clearing my CBS for a few weeks now and it is dropping. However I still get revved up even with 500 mcg methyl b12. It seems like my sulphates are always high first thing in the morning (around 1600) but then right back to normal range for the rest of the day. I can't figure out what's causing them to be high every morning.

500mcg methylcobalamin is still fairly high. It's actually only 1/2 of a normal dose (1000mcg).

My CBS was bad enough, even 1mcg was causing the stress/anxiety reaction.

If your sulfate is going up and down, it seems to me that you're able to process sulfates at least to some extent. Mine was always consistently 1200, then 800 and so on.

 

[Aerose91]

That's interesting, thank you. I guess the conclusion there is that over driving your COMT can cause oxidative damage. That's good to know.

I have been successful at bringing my sulphates down through altering my diet but I can't seem to get them to stay down in the morning, not sure why. I looked up the thrill diet and am going to get even more strict according to that.

Once sulphates are lowered though does that mean we have to maintain that diet indefinitely? The mutation is there so I don't see why we would start processing sulphates all of a sudden.

 

[caledonia]

That's interesting, thank you. I guess the conclusion there is that over driving your COMT can cause oxidative damage. That's good to know.

I have been successful at bringing my sulphates down through altering my diet but I can't seem to get them to stay down in the morning, not sure why. I looked up the thrill diet and am going to get even more strict according to that.

Once sulphates are lowered though does that mean we have to maintain that diet indefinitely? The mutation is there so I don't see why we would start processing sulphates all of a sudden.

No, once they're lowered you can drop the diet. Heartfixer says to keep doing the supps for another month. Then you can drop those, except for some molybdenum for maintenance, so you don't get back in the same boat you were in.

Check with the Heartfixer page to make sure I got all that straight from memory