Methylation Panel Result - What in Yasko’s All-In-One made me feel good?

[Marc_NL]

@Valentijn
Thanks, I will do the 23andme.
I see you're also in NL, do you know why there is such a big price difference between ordering this in the US or Europe ($99 and €169) or is it more or less the same in the US including the shipping (I cannot find the shipping costs on their website).
Edit: I tried the US site and am automatically redirected to the European, so no choice


After following my protocol for two months I will start experimenting a bit more, most of the supplements I already have but not the hydroxoB12, can you advise on a good hB12?

 

[Valentijn]

I see you're also in NL, do you know why there is such a big price difference between ordering this in the US or Europe ($99 and €169) or is it more or less the same in the US including the shipping (I cannot find the shipping costs on their website).

The extra 70 euros is for shipping to the US, and is included in the 169 euro price tag. Customers used to ship them directly to the US from Europe, but now they have a distribution center in the Netherlands where the European samples get mailed before being flown to the US in bulk.

can you advise on a good hB12?

For a sublingual one I really liked Bloem Recovery Power Vitamine B12: https://www.bloem.net/recovery-power-vitamine-b12 . I took 1-4 per day, though not too late in the day since it could make it hard to sleep.

 

[Marc_NL]

Like some of you suggested (@Sherpa @caledonia @Valentijn) I did the 23andme.
Hopefully some of you can share your suggestions (or would it be better to place this in the other section in the forum)?

I got my results last week, since then trying to read and understand information regarding SNP’s but still a bit overwhelmed. I think it will take a lot more time before I can make something useful out of it.

Hope some people can point me in the right direction of what makes sense and what doesn’t.
Which SNP’s do you consider to have some impact and are worth exploring further?
How to find out if I should look for just the homozygous or also specific combinations of heterozygous SNP’s?


So far only some general point from the Genetic Genie website based on my SNP’s:

MTR A2756G, MTRR A66G, MTRR H595Y, MTRR K350A, MTRR R415T, MTRR S257T, and MTRR A664A all work together to convert homocysteine to methionine.
To work properly, methionine synthase requires B12 (specifically in the form of methylcobalamin). An MTR A2756G mutation increases the activity of the MTR gene causing a greater need for B12 since the enzyme causes B12 to deplete since it is using it up at a faster rate. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency.

With a COMT + status, it has been clinically observed by physicians that people may have trouble with methyl donors.

It has been clinically observed that the body may have trouble tolerating methyl donors with a COMT V158M + and a VDR Taq + status.

So according to the MTR/MTRR SNP’s I would need more mB12 but since I have “COMT V158M + and a VDR Taq” I don’t tolerate it? (this which is more or less my experience also after one try, I’m taking hB12 and will try to add some aB12 later).

I also read that MTHFR C677T helps with the conversion from folic acid to methyl folate, does that als count for the conversion from folinic acid to methyl folate since I am taking folinic and Methyl folate both now. Does it mean to better skip the folinic all together?


How does it work with the Detox SNP’s, for example I am homozygous for CYP1A2 164A>C
In caledonia’s SNP guide I see:

CYP1A2 (CYP1A2 164A>C )– no mutations means a fast caffeine metabolizer, one or two mutations means a slow caffeine metabolizer. Some drugs such as acetaminophen are also metabolized by this pathway, as well as polycyclic aromatic hydrocarbons (PAHs).
http://en.wikipedia.org/wiki/CYP1A2

Is it better not to use all the foods mentioned (coffee I can not drink anyway) that you’re homozygous for?
What about heterozygous SNP’s?

The GSTT1 being absent is not good news I think.

@Valentijn
I also put my results in your program “Genes Analysis” resulting in 104 SNP’s against the 1% database (see attachment).
Can you say something about the result or is the idea to just take them one by one and start looking for clues?

=================================================
Methylation Profile:
4 have no mutations (-/-)

homozygous (+/+)
COMT V158M
COMT H62H
AHCY-01
AHCY-19

heterozygous +/-
VDR Bsm
VDR Taq
MTHFR C677T
MTHFR 03 P39P
MTHFR A1298C
MTR A2756G
MTRR A66G
MTRR K350A
MTRR A664A
BHMT-02
BHMT-08
CBS A360A

Not genotyped
MTRR H595Y
MTRR R415T
BHMT-04
AHCY-02
CBS N212N
SHMT1 C1420T

Seems like a lot of SNP’s are not genotyped, is that because of the test (method) or a bad DNA sample, could they be available with doing the same test again?

=================================================
Detox Profile:
homozygous (+/+)
CYP1A2 164A>C

heterozygous +/-
CYP1B1 L432V
CYP1B1 R48G
CYP2C9*2 C430T
CYP2D6 S486T
CYP2D6 2850C>T
SOD2 A16V

Absent
GSTT1
=================================================

 

[Valentijn]

@Valentijn
I also put my results in your program “Genes Analysis” resulting in 104 SNP’s against the 1% database (see attachment).
Can you say something about the result or is the idea to just take them one by one and start looking for clues?

The ones starting with an "i" or under 1% prevalence are usually the most interesting.

 

[caledonia]

I got my results last week, since then trying to read and understand information regarding SNP’s but still a bit overwhelmed. I think it will take a lot more time before I can make something useful out of it.

Hope some people can point me in the right direction of what makes sense and what doesn’t.
Which SNP’s do you consider to have some impact and are worth exploring further?
How to find out if I should look for just the homozygous or also specific combinations of heterozygous SNP’s?

They all count. Homozygous are worse, and heterozygous are, say, half as worse. Pay attention, that while most are downregulations, some are upregulations.

So far only some general point from the Genetic Genie website based on my SNP’s:

So according to the MTR/MTRR SNP’s I would need more mB12 but since I have “COMT V158M + and a VDR Taq” I don’t tolerate it? (this which is more or less my experience also after one try, I’m taking hB12 and will try to add some aB12 later).

The COMT might make it hard to tolerate many methyl groups. You can buffer things by using a less active form, or taking a small amount niacin along with it, as well as keeping the amounts low.

I also read that MTHFR C677T helps with the conversion from folic acid to methyl folate, does that als count for the conversion from folinic acid to methyl folate since I am taking folinic and Methyl folate both now. Does it mean to better skip the folinic all together?

Some people tolerate folinic and some don't. If you're ok with it, you can continue to take it. Folinic helps with DNA and RNA synthesis, so if you can take it, so much the better.

How does it work with the Detox SNP’s, for example I am homozygous for CYP1A2 164A>C

The detox SNPs aren't linked to methylation per se, but they do help explain why you might have issues with certain medications and if you need take special care to avoid certain toxins.

Is it better not to use all the foods mentioned (coffee I can not drink anyway) that you’re homozygous for?
What about heterozygous SNP’s?

If there are foods which don't process well (such as caffeine) or cause the SNP (enzyme) not to perform well, it's best to avoid that food. If you want, you can trial avoiding the food and seeing if you feel better, then doing the food again and see if you feel worse.

For example, I'm hetero for the gluten SNP (shown on Sterling's App), but I feel much better without gluten.

In other cases, there may be foods you should be eating, such as cruciferous veggies.

The GSTT1 being absent is not good news I think.

Yes, it's not good - add that to your homozygous MTHFR and all your B12 SNPs - you probably don't have much glutathione.

Seems like a lot of SNP’s are not genotyped, is that because of the test (method) or a bad DNA sample, could they be available with doing the same test again?

23andme doesn't offer everything that the Yasko test does (which is what the Genetic Genie methylation profile is based on), and every time they go to a new V-chip, the offerings might change.

 

[Valentijn]

They all count. Homozygous are worse, and heterozygous are, say, half as worse. Pay attention, that while most are downregulations, some are upregulations.

No, they don't all count. A lot included in the Genetic Genie report (based off of Yasko) have no impact at all. Some +/+ homozygous are therefore not harmful or are even beneficial. And you simply cannot predict that +/- has about half the impact of +/+. While it does work that way on some genes, such as MTHFR, it is completely untrue for SNPs on other genes, such as MTRR.

In the context of the Genetic Genie report, there are no SNPs listed with harmful upregulations.

Yes, it's not good - add that to your homozygous MTHFR and all your B12 SNPs - you probably don't have much glutathione.

The glutathione transferase genes do not result in low levels of glutathione. Rather, GSTT1 is used to facilitate the use of glutathione in processing specific toxins. With that gene being absent (probably best to double check on https://www.23andme.com/you/explorer/gene/?gene_name=gstt1 ) glutathione levels should still be normal or even high, due to it not being used as much as it typically would.

 

[Lynn_M]

Valentijn,

What is the degree of impact of heterozygous MTRR genes?

Do you know of any measures a person could take to boost their glutathione conjugate functionality if a person was homozygous (+/+) for glutathione transferase genes (in my case, GG for GSTP1)?

 

[Valentijn]

What is the degree of impact of heterozygous MTRR genes?

Heterozygous MTRR missense mutations have no impact unless there are two of the big ones on opposite strands (one from each parent).

Do you know of any measures a person could take to boost their glutathione conjugate functionality if a person was homozygous (+/+) for glutathione transferase genes (in my case, GG for GSTP1)?

First it depends on the specific SNP. Some SNPs have little or no impact, even if some idiot at Nutrahacker or Yasko is marking them as being +/+. Increasing glutathione might help increase the effectiveness of GSTP1 or other glutathione transferase genes, by increasing the likelihood that the existing GSTP1 will hook up with glutathione to do its job.

A lot of people seem to react very badly to directly taking glutathione, either orally or by IV. But glutathione has three basic components: cysteine, glutamate, and glycine. Supplementing one or more of those, if low, might increase glutathione levels and the effectiveness of the existing glutathione transferases. But increasing glutathione would not help with GSTT1 or others if that gene doesn't exist ("absent") or doesn't produce a functional enzyme at all.

Usually it is cysteine which is low, but sometimes it's glycine, or both cysteine or glycine. I've never heard of anyone having low levels of glutamate. So supplementing N-acetylcysteine (NAC) and/or glycine could potentially raise glutathione levels. And it might help with glutathione transferase issues. But that is all speculation based on the biochemical pathways involved, and might not hold up in the real world.

 

[Marc_NL]

@Valentijn, thanks:

The ones starting with an "i" or under 1% prevalence are usually the most interesting.

Do you mean these?
SNP CHRM RARE PERCENT GENOTYPE ETC
rs1838484 4 T 0.00 CT
rs3025051 6 G 0.46 GT
i3003575 8 T 0.14 CT rs56379106
rs2227579 10 T 0.18 CT
rs11656317 17 C 0.32 CT
rs914 17 C 0.09 CT
rs16982149 19 C 0.14 CT
rs28371717 22 A 0.32 AC

With that gene being absent (probably best to double check on https://www.23andme.com/you/explorer/gene/?gene_name=gstt1 ) glutathione levels should still be normal or even high, due to it not being used as much as it typically would.

This is what 23andme says, what does that mean?

Heterozygous MTRR missense mutations have no impact unless there are two of the big ones on opposite strands (one from each parent).

What are the big ones, what does this mean for my MTRR SNP's?



What do you consider, according to your experience, to be the main SNP's (most impact) to follow up in the list I posted before, or do I need to present them in an other form to be able to say anything about that?

 

[Valentijn]

Do you mean these?

Yup. I'll take a look at those tonight and try to post a bit more about them in an hour or two.

This is what 23andme says, what does that mean?

One of the SNPs is definitely present, so it looks like the GSTT1 gene is not absent for you. The report which said it is absent might be going off a list from an older 23andMe V3 chip, when it used to test more/different SNPs.

What are the big ones, what does this mean for my MTRR SNP's?

rs1801394 (A66G), rs1532268 (S202L), i5003808 (S454L, rs137853062). Not sure if they're all still tested on the current V4 chip.

What do you consider, according to your experience, to be the main SNP's (most impact) to follow up in the list I posted before, or do I need to present them in an other form to be able to say anything about that?

Based on the Genetic Genie results, the only thing I see which has much of an impact is MTHFR C677T +/- with MTHFR A1298C +/-. Depending on whether or not you got each of those mutations from different parents, your folate production might be at either 30% or 65% of optimal. Average in the general population is about 68% of optimal.

So you might be "normal" or quite a bit below normal, but we can't tell which from the 23andMe data. At most, it suggests that you might want to be sure to get enough folate in your diet, or a normal amount from a supplement/multivitamin in the active form.

 

[Valentijn]

rs1838484

This isn't on or near a gene, so probably doesn't have any impact.

rs3025051

This is on the VEGFA gene, which is involved with the growth of vascular endothelial cells. There's been no research into this specific SNP on the gene, so no way to know if it doesn't anything. It isn't located on the exon (protein coding part of the gene), so probably couldn't have a large impact, though it's possible it's somewhat regulatory for the gene.

i3003575 rs56379106

This is a missense mutation on the NAT1 gene, which is involved in drug metabolism and the breakdown of folate, typically an up-regulation of both I think. There's no research into this specific SNP, but if we look at the amino acids being substituted in the enzyme created, it's a change from arginine to tryptophan. Those are two drastically different amino acids which have very different structures and behavior, scoring -3 on a BLOSUM62 substitution matrix where the worst possible score is -4 on a scale basically from -4 (most drastic change) to 4+ (no change).

So it might be capable of having an impact, and it sounds like mutations on that gene have a milder impact when heterozygous. But there's not much research into this gene in humans I think.

rs2227579

This is on the UTR regions of both the PLAU gene, and an unidentified gene reading in the opposite direction. So it's possible it could have a regulatory impact, but there's no research into this specific SNP.

rs11656317

This isn't on or near a gene, so probably doesn't have any impact.

rs914

This is the UTR-3 region of TRIM37, so might have a regulatory impact. But no research into it, so there's no way to know. Disorders associated with the gene look like they have to result from homozygous or compound heterozygous mutations, but yours is just heterozygous so shouldn't cause problems in any event.

rs16982149

This is a missense mutation on the SULT2B1 gene, which is involved in speeding up the formation of some hormones and neurotransmitters. A leucine amino acid is replaced by serine on the enzyme which the gene creates, which scores a -2 on the BLOSUM62 matrix. So it could be having a significant impact, though there's no indication if heterozygous mutations are sufficient to cause problems, or if it has to be homozygous.

rs28371717

This is a missense mutation on the CYP2D6 gene, which is involved in metabolizing about 25% of drugs. There's been no research into the impact of this SNP, but the mutation results in the substitution of alanine with serine, a somewhat similar amino acid, scoring +1 on a BLOSUM62 matrix. So probably not capable of causing problems.

 

[Sea]

One of the SNPs is definitely present, so it looks like the GSTT1 gene is not absent for you. The report which said it is absent might be going off a list from an older 23andMe V3 chip, when it used to test more/different SNPs.

This gene can have a partial deletion, I don't know what the consequences of that are. It does have quite a bit of research on it though.

 

[Valentijn]

This gene can have a partial deletion, I don't know what the consequences of that are. It does have quite a bit of research on it though.

I don't think that can be determined from the 23andMe data, however. They do a ton of no-calls for everyone. Typically that means that they're only testing for all of the SNPs for a few (random?) customers, and the rest are just having one or two tested by the standard chip.

 

[Sea]

I don't think that can be determined from the 23andMe data, however. They do a ton of no-calls for everyone. Typically that means that they're only testing for all of the SNPs for a few (random?) customers, and the rest are just having one or two tested by the standard chip.

For everyone? I'm not sure that's the case, or do you know how we could find that out? A deletion or partial deletion is very common for this gene, so I would have presumed lots of no calls would infer a deletion. There are PR members who have had full results for this gene on their 23andme results.

 

[Valentijn]

A deletion or partial deletion is very common for this gene, so I would have presumed lots of no calls would infer a deletion.

There are three patterns in the results for the V3 chip: all null, the same 2 results, and results for every SNP. There's no variations from these patterns. The SNPs which are no-call for people with 2 SNP results are not associated with deletions as far as I can see. The only deletions shown on the gene are pretty typical: 2 indels each 2 alleles long, far away from exons. And 23andMe doesn't include those in the testing.

5 out of 31 ME patients and 5 out of their 31 ethnically matched controls show no results at all on the V3 chip. That's a 16.1% rate of an absent gene, which seems in line with the figures I've seen for Europeans (10-15%). If we were to consider the people with only 2 SNPs reported as essentially lacking the gene, that would add 17 to the ME patients and 11 to the controls, resulting in rates of 71.0% for the ME patients and 51.6% for the controls. Those rates are far far higher than has ever been shown in Europeans, so it seems extremely unlikely that they represent serious deletions.