Genetic variants (SNPs) Interpretation Guide

[Jonathan Edwards]

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

For what it's worth , Pam, I think most biochemists would regard what valentijn as saying as making sense and consider that Dr Van K did indeed have no idea what he was talking about. That is certainly my impression. I think it highly unlikely that valentijn's opinion is just one person being quirky. Dr van K certainly had some quirky ideas.

 

[caledonia]

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...

Check out Ben Lynch's methylfolate side effects article, for info on supporting SOD, tolerating folate and sulfur and more.
http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/
http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/
If you want someone (who is not the originator of the thread) to see your post, you have to tag them like this - @caledonia (the @ symbol and then their exact username). If at least the first part of their name is spelled correctly you will see a drop down menu appear where you can select their name.

 

[npeden]

Well, duh. Thanks, Valenotnj.

 

[caledonia]

For what it's worth , Pam, I think most biochemists would regard what valentijn as saying as making sense and consider that Dr Van K did indeed have no idea what he was talking about. That is certainly my impression. I think it highly unlikely that valentijn's opinion is just one person being quirky. Dr van K certainly had some quirky ideas.

Epigenetics is an emerging science, not yet mainstream, but well on it's way to becoming so.

Some people are early adopters and pioneers. Some people have trouble with new ideas until they become well accepted.

 

[Valentijn]

Epigenetics is an emerging science, not yet mainstream, but well on it's way to becoming so.

Some people are early adopters and pioneers. Some people have trouble with new ideas until they become well accepted.

The problem is that other people equate "making stuff up with no rationality or scientific support" with "scientific pioneering".

Yasko is clearly in the "making stuff up" category, regarding most of her claims regarding SNPs. And Lynch, Heartfixer, and other hangers-on are just repeating the random stuff that Yasko is making up.

 

[Valentijn]

I think most biochemists would regard what valentijn as saying as making sense and consider that Dr Van K did indeed have no idea what he was talking about.

To be fair, Richard didn't say a lot regarding SNPs. It was something he was a bit interested in and inquiring about. He had some involvement with Yasko regarding methylation, but at a pretty general level ... as a theory, and not involving her specific claims regarding SNPs. He was also very up-front in acknowledging that methylation benefits did not last in the study he co-authored.

I think his work gets taken out of context here by people who are trying to use the logical fallacy of "appeal to authority" to support their own pet theories. His approach was open-minded, investigative, humble, and not at all dogmatic. I wish that those who try to use his reputation to prove a point had learned that from him while he was still with us.

 

[bertiedog]

To be fair, Richard didn't say a lot regarding SNPs. It was something he was a bit interested in and inquiring about. He had some involvement with Yasko regarding methylation, but at a pretty general level ... as a theory, and not involving her specific claims regarding SNPs. He was also very up-front in acknowledging that methylation benefits did not last in the study he co-authored.

@Valentijn and @Jonathan Edwards Actually it wasn't Yasko that influenced Rich's original thinking and research, it was people like Dr Jill James and Dr Richard Deth who appear to be extremely well qualified individuals on the subject of Epigenetics and could hardly be regarded as "quirky" I think you will agree .

You can read about Dr James here - https://en.wikipedia.org/wiki/Jill_James and Dr Deth here -https://en.wikipedia.org/wiki/Richard_Deth.

Pam

 

[Helen]

In a seminar, 2011, Dr. Rich V Konynenburg also talked about SNP´s and a possible genetic predisposition to ME/CFS and his view on Dr. Yasko´s work. Below are his own words and voice on this:

Slides, 13 and 14:
http://iaomt.media.fnf.nu/networks/iaomt/IAOMT_talks_Rich_Van_K._2011__Part_1R.pdf

19:44 - 25:17 :
http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/${weburl}

 

[heyitisjustin]

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.

I've heard this suggestion be disputed, saying that drinking didn't matter. They said you could drink but if you want to be overly cautious don't drink 30 minutes before or after meals.

 

[mmssss]

Hello, could you please summarize my 23andme raw data? I have read through your forums and blogs. Still needing help. Thank you~
comt v158m aa ++
comt h62h tt ++
vdr taq aa ++
mthfr a1298c gg ++
cbs c699t ag +-

cyp1b1 L432v CG +-
cyp2c19*17 CT +-
cyp2e1*1b 9896c>g CG +-
gstp1 I105v AG +-
sod2 a16v AG +-
nat2 I114T CT +-
nat2 R197Q AG +-
nat2 K268R AG +-​

 

[alicec]

In the first group of SNPs, the first COMT and the MTHFR SNP do slow the activity of the enzyme. Both however are extremely common. Many millions of people live with these variants and they are not the cause of disease. In some circumstances they may make a small contribution.

Magnesium and vitamin B2 are the cofactors for the respective enzymes so ensuring you have an adequate supply of these will help stimulate the enzymes.

The other SNPs have little or no effect.

With the detox SNPs, often it is combinations rather than individual SNPs which are important, especially for CYP and NAT2 genes. If you run your data through Promethease you may get some insight into relevant combinations.However 23andme doesn't always test enough SNPs to get clear results, especially for CYP 2D6.

That GSTP SNP does cause a little slowing of the enzyme but +/- would have very little consequence.

There are conflicting reports about that SOD2 SNP. Some say GG is detrimental, some that it is advantageous. In other words, there is not much consequence one way or the other and with AG even less so.

 

[mmssss]

thank you so much alicec. I do appreciate it and will look into it further. ~M

 

[caledonia]

Hello, could you please summarize my 23andme raw data? I have read through your forums and blogs. Still needing help. Thank you~
comt v158m aa ++
comt h62h tt ++
vdr taq aa ++
mthfr a1298c gg ++
cbs c699t ag +-

cyp1b1 L432v CG +-
cyp2c19*17 CT +-
cyp2e1*1b 9896c>g CG +-
gstp1 I105v AG +-
sod2 a16v AG +-
nat2 I114T CT +-
nat2 R197Q AG +-
nat2 K268R AG +-​

Sorry for the delay in replying. At this time, I suggest using Ben Lynch's info for the methylation SNPs. You can either run your SNPs through his Strategene report, which gives detailed info (costs $45 I think). And/or use his new book "Dirty Genes" which explain how epigenetics (environment) affect 7 important genes (regardless of SNPs) and what you can do to clean up those genes so they function better.

The detox section of the SNPs Interpretation Guide is still relevant.

MTHFR A1298C is less significant the MTHFR C677T. You can do the quiz in the Dirty Genes book to see if it's having a negative effect.

Genetically speaking, COMT and CYP1B1 metabolize estrogen, so if those are running slow, you may become estrogen dominant. There are many adverse things which can happen if that's the case. Cruciferous veggies or supplements based on those, like DIM, can help.

A slow VDR can make you deficient in vitamin D, so it would be good to test your vitamin D levels and supplement if they're low.

The CBS SNP doesn't seem to be that important in and of itself, however the entire transsulfuration pathway (CBS sits at the top of it) can become screwed up due to mercury and arsenic. That can affect SUOX and cause sulfur issues, use up glutathione, and cause issues with taurine.

CYP2C19 seems to be an upregulation which can cause issues with proton pump inhibitors and various psych drugs. Slower acting versions might work better.

CYP2E1 detoxifies nitrosamines (beer, cured meats, and dried, smoked or salted fish), ethanol (acetaldehyde), and anesthetics, so you could have trouble tolerating those.

GSTP is a glutathione SNP - glutathione is the body's major antioxidant and detoxifier. So it would be good to avoid toxins, and maybe take things to enhance glutathione. Vitamin C is a good generally safe thing for that. Some people can run into trouble with glutathione and NAC supplementation due to the sulfur in them.

SOD - I am confused on this one, as some people report A as the normal allele and some report the opposite. SOD deals with mitochondria and oxidative stress. I would say at this time, if you clean up other major SNPs, SOD will take care of itself.

NAT - detoxifies petrochemicals and a mutation will make it run slow so you don't detoxify as well, so avoid those.

The main takeaway of detox SNPs is to avoid toxins and eat your fruits and veggies for antioxidant protection.

 

[mmssss]

Thank you so much for your informative feedback. I do appreciate it. Yes, I have the Dirty Genes book now and I did put my data into Promethease and a bunch. I was looking for language that I could understand and you did just that!. Take care~

 

[alicec]

Just be cautious in accepting all the SNP claims that proliferate on the internet. See this post.

 

[rosboy]

Hi guys. Hoping someone can help me interpreting my SNPs. I've tried to read up, but an a little confused and brain fog isn't helping!

My results are as follows:

Methylation profile:

VDR bsm +/-
VDR Taq +/-
MAO-A R297R +/+
ACAT1-02 +/-
MTHFR C677T +/-
MTHFR 03 P39P +/-
MTHFR A1298C +/-
MTR A2756G +/-
MTRR A66G +/+

Detox Profile (not sure if this is relevant)

CYP1A2 164A>C +/+
CYP1B1 L432V +/-
CYP1B1 N453S+/-
CYP2D6 S486T +/+
CYP2D6 2850C>T +/-
NAT2 R197Q +/+

Screenshots of the results are attached.

I'm currently about 1 month into the freddd protocol. I've seen minor results, enough to encourage me to keep going.

Any feedback on the SNPs would be greatly appreciated.

Thanks

 

[caledonia]

Hi guys. Hoping someone can help me interpreting my SNPs. I've tried to read up, but an a little confused and brain fog isn't helping!

My results are as follows:

Methylation profile:

VDR bsm +/-
VDR Taq +/-
MAO-A R297R +/+
ACAT1-02 +/-
MTHFR C677T +/-
MTHFR 03 P39P +/-
MTHFR A1298C +/-
MTR A2756G +/-
MTRR A66G +/+

Detox Profile (not sure if this is relevant)

CYP1A2 164A>C +/+
CYP1B1 L432V +/-
CYP1B1 N453S+/-
CYP2D6 S486T +/+
CYP2D6 2850C>T +/-
NAT2 R197Q +/+

Screenshots of the results are attached.

I'm currently about 1 month into the freddd protocol. I've seen minor results, enough to encourage me to keep going.

Any feedback on the SNPs would be greatly appreciated.

Thanks

At this time I suggest that people get a copy of Ben Lynch's book "Dirty Genes" to assist with methylation cycle SNPs. The book emphasizes epigenetics (environment) over genetics. There are some additional genes like PEMT which are also important. There is a lot which can be done with foods and avoiding various toxins. Supplements are more like icing on the cake if the other measures aren't helping.

It looks like your tendency is to run slow with vitamin D - might want to get your levels tested and supplement if necessary. You might also need some folate and B12 if your genes are dirty and you've tested low or you're having deficiency symptoms. Your MAO A has a tendency to run fast.

The people in my family who have ACAT have had kidney stones and the ones without it don't. Bile support can be helpful.

For the detox SNPs:
CYP1A2 detoxifies caffeine, acetaminophen, polycyclic aromatic hydrocarbons (PAHs). Yours runs slow.

CYP1B1 metabolizes estrogen - can cause estrogen dominance, which can cause estrogen related cancers such as breast or uterine cancer in females, and prostate cancer in males. You can eat cruciferous veggies, or take DIM or IC3 (components in cruciferous veggies) to lower estrogen if you've tested, and it's high. Calcium D glucarate is another option.

CYP2D6 - detoxifies ~20-25% of all prescription drugs including tricyclics, MAOIs, SSRIs, opiates, anti-arrhythmics, beta- blockers, Cimetidine, etc. Yours runs slow.

NAT - detoxifies petrochemicals. People with NAT problems can be chemically sensitive to chemicals like perfume, gasoline, toluene, xylene i.e., multiple chemical sensitivity. Increased risk for developing lung, colon, bladder, or head & neck cancer. Yours runs slow.

General advice for detox SNPs:
Don't smoke, and avoid second hand smoke and chemicals, especially the chemicals detoxified by your slow running SNPs. If you must take one of the medications mentioned, you might need less of it than other people. Eat your fruits and veggies, especially cruciferous veggies, to help detoxify.

If you follow the advice in the Dirty Genes book, it should help the detox SNPs as well.

 

[rosboy]

@caledonia, Thanks for taking the time to respond. Your post was very useful, and I really appreciate it. I've bought the Dirty Genes audiobook, and started listening to it. Hopefully it helps!

 

[alicec]

I've bought the Dirty Genes audiobook, and started listening to it. Hopefully it helps!

Be careful with that - see this and this post plus other links in my post above.

 

[rosboy]

Be careful with that - see this and this post plus other links in my post above.

Thanks Alicec. I always appreciate opposing views on subjects, and will investigate further.