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My SNPs: weirdness explained

WoolPippi

Senior Member
Messages
556
Location
Netherlands
Here are my results from Genetic Genie.

It shows my sensitivity to all kinds of metals. It explains why I react fiercely to a normal dose of mB12 (I need much lower dosage, about a fifth of normal). It makes it logical that I feel so much better since I upped my vit D to 3000 IU/75 mcg per day.
It explains why I have such excitatory neurons and overall brain chemistry (thank you sluggish MAO A).

Does it also explain why I naturally stay away from sulphurous foods? Why my Zinc was low and triggered a massive Cu dump when I supplemented? Why vegetable oil makes me antsy? Is my liver under strain?
Is there anything else you notice?
Please share your thoughts :)

calling @Gondwanaland and @Helen
Gondwanaland, I misread one of my snps, I do not have a homozygous CYP1A2 164 A>C
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Gondwanaland

Senior Member
Messages
5,092
Does it also explain why I naturally stay away from sulphurous foods?
Does it? I have tried not to pay to much attention to my +/- SNPs, not because I don't think they don't have a cummulative effect (they certainly do), but because I get overwhelmed from too much information. My brain just doesn't cope with it. And when I tried I low thiol diet I felt much worse.
It makes it logical that I feel so much better since I upped my vit D to 3000 IU/75 mcg per day.
I will try that for my husband!
It explains why I have such excitatory neurons and overall brain chemistry (thank you sluggish MAO A).
I need to find out what interacts with my +/+MAO-A that makes my reactions so different from yours. I remember reading that you are a happy person, but I have always been a pessimistic person, and have always avoided things that made my serotonin go up, so I have always been in a catch 22 - pessimistic and avoiding things that make me happy. But I don't think I have ever been depressed (only when I supplemented with vit D). Perhaps because I have been magnesium deficient for a long time.
It shows my sensitivity to all kinds of metals.
Which SNPs?
It explains why I react fiercely to a normal dose of mB12 (I need much lower dosage, about a fifth of normal)
Which SNPs?
Why my Zinc was low and triggered a massive Cu dump when I supplemented?
Which SNPs?
Why vegetable oil makes me antsy?
Which SNPs? My husband can't even tolerate olive oil or coconut oil, just animal fat
Is my liver under strain?
Which ones? I have a very hard time trying to tell adrenals and liver symptoms apart!
Is there anything else you notice?
Sorry, I have only questions and no answers today, I woke up feeling dumb :grumpy:
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
@WoolPippi -

I got my 23andme results today! :D :D :D

Unfortunately, I'm having some problems with the program to discern what SNPs are rare. :( I'm also sorry to say that it appears that one of the SNPs I was really waiting for isn't included on 23andme.

On the bright side, I do know that I am 2.7% Neanderthal. ;)

I agree with @Gondwanaland - can you explain your conclusions? I know we'd appreciate it.

-J
 

WoolPippi

Senior Member
Messages
556
Location
Netherlands
O my, you all want me to show off my ignorance now, right? Serves me right, I did put bold statements in the post. :rolleyes:
Well, here goes. This is my simpleminded interpretation, a working theory for my daily life.

First off: a faulty SNP doesn't mean the whole enzyme it codes for is faulty (I think. I'm not even sure anymore)
More often then not there are other enzymes dabbling in the same function. So: don't panic, it's usually not a white/black situation.
I'm mainly interested in the enzymes and their functions. There's a lot we don't know yet. A lot.

I'm working with these two diagrams to broadly understand how the cycles work in my cells. They both represent the same processes and they concern both the energy supply of cells as well as getting rid of toxins and stuff the cell doesn't need anymore. Once I studied them intensely and understood them. Now I've forgotten. Sources are Yasko, Heartfixer and AutismNTI.

The top one shows the five "separate" cycles that feed of one another.
The lower one shows basically the same but shows which metals frustrate which step. For example at the orange enzyme called DHPR there's a grey "stopper" called Alum.
Don't bother understanding these diagrams if you've never seen them before, just look at them a bit, notice enzymes and products and then move on.

upload_2015-4-5_14-56-36.png



upload_2015-4-5_14-55-17.png

Now I combine my SNPs into this. I only look at the homozygous mutations because heterozygous mutations won't hinder enzyme production too much, I figure. Even homozygous mutations do not mean the resulting enzyme is a total failure. It may just function considerably less.

+/+ MTR A2756G, MTRR A669 are a nice set, frustrating the usual path between the Folate Cycle and the Methylation Cycle (4th and 5th cycle) in a double way. MTR is the enzyme that gathers B12 (and vitD) but it's not working too well. MTRR is a brake that's applied to it because otherwise MTR syphones away all the B12.
My brake is broken, it allows MTR to grab all the B12 it can get hold of and lets it throws it in the bin. Wrapping it in vit D in the proces.

So here I am, having all the symptoms of B12 shortage and vit D shortage even though blood levels look good. MTR/MTRR explains why: I'm expelling B12 and vit D at cell level. And Folate is hardly usable.

But I've read cells find another way to convert folate into the 5th cycle. It's called "the long route". Nevertheless, it tells me my cells cannot properly use the folate in my cells, blood or food. So don't bother eating it. (Metafolin, on the other hand, works like a charm. But I'll get to bypassing enzymes later on.)

So. Leaking vit D huh?
But the enzymes for my Vit D receptors are not whole. My VDR Tag is out and VDR Fok is unknown. There's a high probability my vit D receptors are not too good at their functioning and on top of that vit D gets used up fast through this alternative path way. This coincides with a ridiculous sensitivity to vit D shortage, it will mess up my brain chemistry.

This brings me to the neurotransmitter part of these cycles. They are at the bottom. Dopamine, Serotonine, the lot.
I have a natural tendency to be "quicksilvery." Quick, smart, easily excitable, force full, pushing, confident, intense, concentrated, dominant, multi tasking, survivor in complex situations. Also sunny disposition.
These are all the hallmarks of lots of serotin and dopamine. This coincides with a faulty dismembering enzyme that breaks down these excitatory neurotransmitters. This enzyme is MAO A and I am homoz. for one of its building instructions: MAO A R297R.
(People with ADHD have a MAO A enzyme that works too hard: their happy and concentrating neurotransmitters are broken down too fast, while the person still had use for it.)

I'm not really sure but because the 4th and the 5th cycle are hampered in my case (and some heteroz. snp's are involved in the 3rd and 4th also) I figured excess stuffs that would usually go through the cycles are now more easily thrown away (downwards in the diagrams). Resulting in excess dopamine and serotonin.

Next: I had my hair analyzed and found I had the normal amount of heavy metals. Which is too much. And my blood Zinc was way too low. Looking at the second diagram I saw which metals frustrated which enzyme. I don't understand it fully but I now know Lead and Aluminium are BIG THINGS when cell processes are concerned. Any amount is too much.
With my processes being very vulnerable by the time I got really ill I understood why any vaccin (with Alum carrier) or any lead exposure would wipe me out.

I now also understood why for the first 18 months of my illness I had severe brainfog. (as in: I didn't know my name on most days and didn't care). This was not only due to the metals but when these basic processes fail, you cannot expect your brain to still function. I was also malnourished, at cell level, because there's a full spectrum of amino acids and minerals needed for everything to work optimal.
Once you reach a level of malfunction where everything goes, well, everything goes. There's no robustness left. No reserve. No magic pill either.

When I learned about these cell cycles I drew this conclusion: "not only is my energy supply at cell level hindered, also the means to convert homocysteine into harmless stuffs is hindered. I think my cells are filled to the brim with the toxins they cannot process properly, especially ammonia. And they are lacking full spectrum amino acids and minerals."

This is the strategy I thought up:
  1. don't put any more stress on the cell. No "ammonia-rich-foods".
  2. start supplying the full things: full spectrum mineral supplements and full protein (i.e. egg yoke, gelatine or chicken broth)
  3. the system is totally overwhelmed at the moment. Any little thing is too much now. So stay away from all heavy metals. Get Amalgam fillings out. Stop breathing exhaust fumes. Don't ever pick up stained glass as a hobby again. Stop using aluminium containers and pots and pans (use glass and ceramics instead).
  4. take the time to get rid of the waste the cells have gathered over the years. Work slow.
  5. allow time for new cells to be build. Don't expect results overnight.
  6. preserve energy. Rest. And aid body in waste removal: gently stretch and yawn while you're in your bed all day.
  7. (later on there was the reduction of strain on the nervous systems, what with me possessing easily excited neurotransmitters and stress being a very physical altering modus)(also I educated myself on hormones. Especially vit D, progesteron, cortisol and insuline. You don't want insuline raging through your body, it's a poison)
Think I'm at the end of my post, I think.
I learned to match food I ate to changes is moods. To me, brain chemistry and digestion are much a part of these cell cycles I show here. It has all to do with metals, hormones, neurotransmitters, proteins, any sort of "-ine" floating through the body. Most of them synthesized and broken down by enzymes in cells.

By now, a few years after I came back from the brain fog dead, I think most of my cells are no longer overwhelmed. No longer filled to the brim with ammonia. I've slowly started to aid the methylation cycle with both mB12 and Metafolin. Oei!:wide-eyed: Gotta take it slow. These cycles are jumping at the chance to open up the throttle. I need to have in place: all co-factors, all ways of waste disposal.

Well. This post has taken two hours to write. I forgot if there's anything else I want to say. I'm going to post it and see how it looks. Perhaps edit it a bit. I still haven't learned how to properly insert/upload a .pdf
I'm sure I didn't answer all the questions so feel free to remind me.
 
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Messages
15,786
@WoolPippi - MTR A2756 +/+ results in a mild reduction in homocysteine. It's beneficial, and nothing's getting all sucked down the drain. It's also not that uncommon to be +/+. 5% of the general population is +/+, going up to 15% for some ethnic groups.

VDR Taq is having little or no impact.

I wouldn't put much stock in that MAOA SNP either. It's on a coding part of the gene, which basically just gets translated into proteins. Except it doesn't result in any change of protein. I'd be rather surprised if the same SNP is both coding and regulatory. The psych research into these things tends to be rather sloppy and of low-quality. Nothing to draw conclusions about until they find actual differences in enzyme activity, versus vague and barely significant correlations with personality traits.

And your conclusion regarding homocysteine is a bit odd. It can get converted into glutathione via the cystiathione pathway, which begins with CBS. It can also get converted pretty well via the other pathways. And it's a common and easy thing to get tested in a lab if really worried about it.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
@WoolPippi - your charts are amazing! Thanks for sharing them. I'll be staring at them for some time to come.

@Valentijn - re: the MAOA SNP - mine is +/+. If I'm right in assuming that it would reduce the rate at which I break down serotonin (by looking at WoolPippi's chart - would you agree?) then this mutation has profoundly affected me.

Or perhaps it's something else that makes me super-sensitive to serotinergic compounds, and this mutation coupled with my reaction to serotonin is a coincidence. Trying not to indulge in Post-Hoc thinking!

-J
 

Gondwanaland

Senior Member
Messages
5,092
I think there is an unnecessary polarization regarding the methylation SNPs. They are not mutations, or genetic defects, or genetic diseases.

If you think you can benefit from methylation support, if you have reasons to believe that you are not responding optimally to environmental toxins, you can benefit from the clinical observations and self-experimentation that are the current guidelines for this approach (link in my sig "Freddd's protocol").

My siblings for instance, who probably have SNPs similar to mine, do not need methylation support (nor are PR members o_O). But I, for some reason do.

I em expecting that @Helen will soon talk about this subject as to why some people fare worse than others with same methylation SNPs.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
It is a coincidence to all MAO-Aers ;)

LOL! My body's attempt to balance this is to keep my serotonin very, very low. This actually makes me really glad that they don't measure serotonin to 'test' for depression: the serotonin in your system is low. Here, let's 'patch' that.

Nonono. Bad plan.

I wonder if others with the MAO-A homozygous mutation also tend to have low serotonin to compensate.

My siblings for instance, who probably have SNPs similar to mine, do not need methylation support (nor are PR members o_O). But I, for some reason do.

My mother and my oldest sister both have some flavor of what I've got. It's not quite the same, but similar enough. I'm just the sickest of the three of us right now, and the only one of the three with a scientific bent.

Filling in where I have the most 'issues', everything nestled within a cycle is more or less okay; everything that's 'clean up' as the chemicals leave the cycle is +/+. :( Issues with COMT, MAO A and CBS that seem profound, from my very limited current understanding. For example, I have a homozygous mutation for CBS C699T and a 'no call' for CBS A360A - like it's a deletion. That leaves me with no functioning, measured CBS? There is another CBS SNP that genetic genie mentions, but 23andme doesn't test for it.

I em expecting that @Helen will soon talk about this subject as to why some people fare worse than others with same methylation SNPs.

I hoopppe sooo. I know I only got my results the other day, but I feel pretty lost. Soooo muuuuch daaaata.

-J
 

Gondwanaland

Senior Member
Messages
5,092
I wonder if others with the MAO-A homozygous mutation also tend to have low serotonin to compensate.
I do. And if for any reason something happens that makes my serotonin to raise I must immediately act to screw everything up and get it lower than before :bang-head:
My mother and my oldest sister both have some flavor of what I've got. It's not quite the same, but similar enough. I'm just the sickest of the three of us right now, and the only one of the three with a scientific bent.
I am the only one at my home with problems, and all evidence seems to point to amalgams. my sister had only one amalgam from age 18 thru 22, and my bro never had them. I started getting them at 8-9 yo and kept getting them for many years, then some unsafe replacements and still have 5 in my mouth.

Apparently some have been put there just because of acidic demineralization and not bacterial cavities. No dentist ever suggested I should use alkaline tooth paste :mad: Now that I have been brushing my teeth with calcium carbonate and magnesium oxide only for almost one year I have experienced remineralization of old missing enamel chunks.
I hoopppe sooo. I know I only got my results the other day, but I feel pretty lost. Soooo muuuuch daaaata.
Have you already found caledonia's documents? They are really helpful and are linked in my sig under "Freddd's protocol" (did I ask you this before? :confused::alien::sluggish:)
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
I must immediately act to screw everything up and get it lower than before

HOW DO YOU DO THAT, because, funny story, I was having seizures this one time...

I am the only one at my home with problems, and all evidence seems to point to amalgams. my sister had one amalgam fro mage 18 thru 22, and my bro never had them. I started getting them at 8-9 yo and kept getting them for many years, then some unsafe replacements and still have 5 in my mouth.

I resist simple explanations such as these, but I've also had a ridiculous amount of dental work. My Dad too - I was told it was 'hormonal' when I started getting tons of them at puberty. :( I really don't get them that often anymore - it's mostly in replacing the ones that are there and broken-down.

Have you already found caledonia's documents?

I've kept passing them by. I might have started at the wrong place, but when my homocysteine levels were normal, I more or less gave up on affecting them (why should I?) and continued taking massive amounts of B12 and folate, which are helpful to me.

Re the SNPs and their meaningfulness:

So I'm reading Mark London's CBS Upregulation: Myth or Reality?

And I see this:

"The polymorphism with the greatest effect, as shown by the PML test, was found to be 699CàT (Y233Y). People with the TT (+/+) genotype of that polymorphism, and to a lesser degree CT (-/+), produce lower levels of homocysteine levels in response to the PML test, when compared with the CC (-/-) genotype. Lower homocysteine levels from that test infers greater CBS activity. By the way, none of these genotypes are rare. About 40% of the population has CC, 40% has CT, and 20% have TT. Thus, all the genotypes of this polymorphism are quite common."​

Okay, is that information really accurate - I mean, can it even be? My base-pair for that SNP (CBS C699T) is AA, but it didn't show up as rare. Presumably if everyone is either TT, CT, or CC, then my AA is a really, really rare combo, but it doesn't show up as so on Valentjin's program set up to catch rare SNPs.

:woot: Lightbulb moment. Oh my GOSH, when you were saying 'it's not like they're mutations...' Ugh, my brain. Okay, so the three possible combos are TT, CT, or CC. There's one homozygous that is considered 'best' for functionality; then heterozygous; then homozygous of the 'undesirable' base being least functional. But if you have none of those three options, then you have a mutation. So, is this right that in my case, AA is a mutation?

Reaching back, back into the dark recesses of Biology 101, that doesn't necessarily mean a nonfunctional gene or even any change at all. Sometimes, if you substitute a base pair, you're still coding for the same amino acid, because this kind of failsafe is worked into the genome. Sometimes you code for another amino acid, but it's not enough to significantly disrupt the structure of the protein. So it doesn't matter.

It's only when a mutation causes a significant screw-up in the protein that the results are significant.

If the rest of you are going :bang-head::bang-head::bang-head: and thinking this is obvious? (Or incorrect? :vomit:) I am older than I look, and it's been...... fifteen years since I discussed genetics in any meaningful way before coming here and needing to know. Stuff is coming back, but sometimes it's a little slow in the coming. And maybe the slow unspooling of my thoughts is making someone else have an a ha! moment. We can all hope.

There are still some pages that I've started reading here and gone, wait... I don't understand this, yet, and closed the window.

-J
 
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Gondwanaland

Senior Member
Messages
5,092
HOW DO YOU DO THAT
I can share something I used to do when I was a child: in family moments when mom wanted to hug and snuggle with her children I would run away :oops: while my sibs would stay and hug and snuggle back and enjoy the love :love:
I resist simple explanations such as these, but I've also had a ridiculous amount of dental work.
Just another coincidence ;)
Re the SNPs and their meaningfulness
I was really talking about the regular combos and their different effects that can be considered when addressing methylation. I don't think it matters they being common. As I said, my sibs may share identical SNPs with me, but for them it dosen't matter, since they are not ill. But for me it is a huge difference if an enzyme is up or downregulated, even if it is pretty common. My body can't cope as easily as my sibs' with these small disadvantages.

Now about real mutations, I haven't run my data thru Val's software yet, so I don't know about my rare SNPs. My common ones are already a handful for me :ill:

I hope she can reply to your questions about mutations, I am sorry, I haven't looked into it yet...
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
I hope she can reply to your questions about mutations, I am sorry, I haven't looked into it yet...

No problem! I was hoping you were talking about a supplement that reduced your serotonin levels. I have found that there are other chemicals that increase the rate at which serotonin is processed (the opposite of an SSRI) but frankly I'm too frightened to try. I'd only need something like that in an emergency situation, and in an emergency, the last thing you want to do is make anything worse!

I'm running through my 1% SNPs, but there are over 100 of them, and it's slow going. (Slog... slog... sloggggg)

Thanks for all your input, though! <3

-J
 

pogoman

Senior Member
Messages
292
......Okay, so the three possible combos are TT, CT, or CC. There's one homozygous that is considered 'best' for functionality; then heterozygous; then homozygous of the 'undesirable' base being least functional. But if you have none of those three options, then you have a mutation. So, is this right that in my case, AA is a mutation?


-J

23andme can report allele's (C, G, A, T) different from medical/scientific literature but basically A is same as T, C is same as G.

https://customercare.23andme.com/hc...strand-does-23andMe-report-for-SNP-genotypes-

For example, 23andMe might report that a SNP has two versions, G and A. But other sources may report that the versions are C and T. Because of the double-stranded nature of DNA, both ways of reporting the SNP are correct: G pairs with C on the opposite DNA strand, while A pairs with T.

I would also recommend running your 23andme results thru Sterlings App V2, it covers much more SNPs than genetic genie.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
.....seriously, @pogoman? UGH. Yes, that much freshman Biology I do remember... Adenine pairs with thymine. :( But this still makes me feel disgruntled. :(

So a TT is an AA, essentially. Gotcha.

However, if it were, say, AT, that would have to be a mutation, since the inverse (TA) is not a suggested base pair?

Thanks for clearing that up. I feel a bit silly, now...

Sterling's App is $30, which isn't exorbitant. Still, I do hope you're right and it's worth it. :)

-J
 

pogoman

Senior Member
Messages
292
@JaimeS lol, I am a truck mechanic and into computers so I use the mnemonics Auto Transmission and Computer Graphics to remember the allele pairing.

on the different analyzing services, I've used GG, Promethease and Sterlings.
The GG recommendations for my bad SNPs were vague and did not help in developing my personal protocol that has helped me immensely with my pain and fatigue issues.

Only Sterlings reported on TCN2 which involves B12 transportation into cells.
It also complicates MTHFR C677T and I am homozygous for both, I take high quantities of B12 and folate along with lithium and mitochondrial factors and I am soooooo much better than just two months ago.
as a comparison, my Sterling V2 report is 42 pages in pdf format, 34 pages are all SNP results.

I also downloaded Valentijn's rare SNP analyzers but its time consuming checking all of them and not sure how to interprete them anyways.
 
Messages
15,786
@Valentijn - re: the MAOA SNP - mine is +/+. If I'm right in assuming that it would reduce the rate at which I break down serotonin (by looking at WoolPippi's chart - would you agree?) then this mutation has profoundly affected me.

Or perhaps it's something else that makes me super-sensitive to serotinergic compounds, and this mutation coupled with my reaction to serotonin is a coincidence. Trying not to indulge in Post-Hoc thinking!
I'd guess it's something else. I'm -/- for MAOA and also can't tolerate anything involving serotonin either.
 
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15,786
Issues with COMT, MAO A and CBS that seem profound, from my very limited current understanding. For example, I have a homozygous mutation for CBS C699T and a 'no call' for CBS A360A - like it's a deletion. That leaves me with no functioning, measured CBS? There is another CBS SNP that genetic genie mentions, but 23andme doesn't test for it.
It's not a deletion. Deletions are marked with "D". Everyone has no-calls - sometimes because their specific chip didn't test for certain SNPs, and a great deal more which are completely random.

Additionally, a deletion doesn't mean that a gene stops functioning. Deletions are quite common and usually completely harmless.

And finally, CBS A360A does absolutely nothing as far as actual scientific published research is concerned. So if someone's going to claim otherwise, I'd love to see some proof beyond "I have +/+ and I have this problem, ergo the two must be related!"
 
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15,786
Okay, is that information really accurate - I mean, can it even be? My base-pair for that SNP (CBS C699T) is AA, but it didn't show up as rare. Presumably if everyone is either TT, CT, or CC, then my AA is a really, really rare combo, but it doesn't show up as so on Valentjin's program set up to catch rare SNPs.
DNA has forward and reverse strands. Some genes have alleles reported on the reverse strand in most sources, but 23andMe reports on the forward strand for all genes. That source is using the reverse alignment, so TT = AA.
:woot: Lightbulb moment. Oh my GOSH, when you were saying 'it's not like they're mutations...' Ugh, my brain. Okay, so the three possible combos are TT, CT, or CC. There's one homozygous that is considered 'best' for functionality; then heterozygous; then homozygous of the 'undesirable' base being least functional. But if you have none of those three options, then you have a mutation. So, is this right that in my case, AA is a mutation?
No. Usually there are two alleles for every SNP. And in the vast majority of cases, those variations don't make any difference at all. In some cases, they might make a small difference. If there is a variation in the exon parts of the gene, which are the parts which are read to create proteins, it can result in a missense mutation or a nonsense mutation.

If it's a missense mutation, one protein will be swapped with another. This often isn't a big deal, especially if the new protein has similar properties compared to the normal protein. But it can have a significant impact if it happens in a place where the protein attaches to other proteins. If it's a nonsense mutation, the variation results in reading a "stop" codon (three SNP combination) instead of a protein. Nonsense mutations can have a huge impact, because then the rest of the protein is not created. If it happens early in the protein, there might be no gene function at all.

CBS C699T is not a missense mutation or a nonsense mutation. While it may possibly have more impact than the other (meaningless) Yasko CBS SNPs, it's still quite mild - in the neighborhood of a 5% upregulation of the CBS gene when +/+. That results in mildly lower homocysteine, and it is shown to be associated with reduced risk of various disease.