My Yasko SNPs

[Valentijn]

Someone asked, so here they are, with my commentary
HOMOZYGOUS:
VDR Taq (rs731236)
MTRR A66G (rs1801394)
CBS A360A (rs1801181)

HETEROZYGOUS:
COMT V158M (rs4680)
COMT H62H (rs4633)
MTHFR 03 P39P (rs2066470)
MTHFR A1298C (rs1801131)
AHCY 01 (rs819147)
AHCY 02 (rs819134)
AHCY 19 (rs819171)

So I might be a bit low on vitamin D 25 due to the VDR Taq. According to heartfixer, this can cause low dopamine. My dopamine tests pretty normal, though somewhat closer to the low end.

MTRR A66G affects homocysteine (higher) and methionine (lower) levels a bit, which might explain mildly elevated homecysteine levels I had a while ago. Results from last year also show homocysteine on the high end of normal and methionine on the low end of normal. So nothing dramatic going on, but I might benefit from getting things closer to the middle of the range.

CBS A360A is meaningless, so I can ignore that one. According to heartfixer (someone should probably tell them that the 10x up-regulation is horribly wrong - a rather embarrassing mistake to be promoting) it's an upregulation. But my levels of things shown as coming "after" the CBS enzyme are low or normal, not high.

Heterozygous COMT's aren't really a risk. At most it means I'm not breaking down catecholamines particularly quickly or slowly.

The AHCY SNPs listed are meaningless.

MTHFR A1298C without MTHFR C677T shouldn't have much impact on folate levels, if any. Heartfixer says it might cause low BH4. Low BH4 can cause low catecholamines, which might be about half true in my case: low norepinephrine and serotonin, but normal dopamine and high-normal epinephrine. Phenylalanine, which BH4 processes into catecholamines, is normal, not high at all, so that doesn't seem to support the theory of low BH4. Other substances which BH4 breaks down, tyrosine and tryptophan, are quite low for me, barely in the reference range. So if MTHFR A1298C does have an impact on BH4, I'd be surprised if the heterozygous version is at all revelant.

MTHFR 03 P39P does seem to have some sort of effect in a couple studies, but the heterozygous version doesn't make it to a statistically significant level. It's also not clear what the effect actually is.

 

[Bluebell]

Your VDR Taq is the AA homozygous or GG? (I expect it's AA, since you said you are reporting this the Yasko way.)

Gosh, your results look pretty undramatic as far as methylation goes -- not that I really know anything about it, obviously!

You've probably looked at ALL the references already, but this is what I copied and pasted a while back from (apparently, according to my notes) SNPedia about the MTHFR A1298C:
"An MTHFR mutation can starve the entire methylation cycle, which has some very large health impacts.
The C677T mutation is associated with a general set of problems: elevated homocysteine, increase in heart disease, increased stroke, increased deep vein thrombosis, peripheral neuropathy, placental vascular problems (stillbirth), preeclampsia, neural tube defects, cleft lip.
The A1298C mutation is assoicated with a second set of problems: depression, anxiety, irritable bowel syndrome, fibromyalgia, chronic fatigue, migraines, dementia, nerve pain, schizophrenia, parkinson's, tetrahydrobiopterin (BH4) problems. Although not addressed by Yasko, if your Promethease report includes Gs223 or Gs224, you may have additional BH4 impairment.
A person who is compound heterozygous (a single C677T mutation and a single A1298C mutation, each on a different strand) will see symptoms from both defects, but the symptoms tend to be more severe. Rawlins also believes that blood clots are more prevalent."

On a different tangent, in a slap-happy moment, I was considering adding a caption under my image photo:
"More % Neanderthal than 'Adreno', but less hairy", then decided not to. Which was the right call, I think.

I am checking out your profile page, which feels a bit like stalking, and see that you've been baking a loaf of bread since March.

Then I saw your post about your feeling unwell recently - snot sampling and stuff - I'm sorry to hear that.

Happy Monday!

 

[Valentijn]

Your VDR Taq is the AA homozygous or GG? (I expect it's AA, since you said you are reporting this the Yasko way.)

Yup, AA. It's VDR Bsm that is reported backwards, so I just ignore that one since it's replicating the results of VDR Taq anyhow (albeit in reverse).

Gosh, your results look pretty undramatic as far as methylation goes -- not that I really know anything about it, obviously!

Agreed. I think the biggest potential for impact is on my catecholamines. But still, nothing dramatic.

You've probably looked at ALL the references already, but this is what I copied and pasted a while back from (apparently, according to my notes) SNPedia about the MTHFR A1298C:

Yeah, it does seem like it can have some nasty effects, but that's mostly just been documented in conjunction with MTHFR C677T, so probably nothing for me to worry about there. Plus I'm heterozygous, which usually means even less to worry about.

"More % Neanderthal than 'Adreno', but less hairy", then decided not to. Which was the right call, I think.

I am checking out your profile page, which feels a bit like stalking, and see that you've been baking a loaf of bread since March.

It's a very GOOD loaf of bread! Lately we've been experimenting with "Frisian Sugar Bread" (aka Valentijn's Diabetes bread), which is a lot like cinnamon rolls but in bread form. It's what the Dutch get instead of Cinnabon

Then I saw your post about your feeling unwell recently - snot sampling and stuff - I'm sorry to hear that.

Also a rash now with petechiae and striae. Which has actually made it easier to guess at the cause - I'm thinking Bartonella, since the symptoms are a dead match. I might have had it for years before getting sick (if I do have it), because had striae appear suddenly before (without weight gain), quickly followed by neurological symptoms.

Going in to the doc tomorrow to report the additional symptoms and what we think it might be. Then either on to getting it diagnosed through the health system or doing it via a private lab. If I do have it, the right antibiotics might make a big dent in my chronic symptoms. Not holding my breath though

 

[Bluebell]

Oh, is the MTHFR quote I copied above about the homozygous mutations only? I was thinking it was for even the heterozygous versions.

---
About Yasko's reporting of VDR backwards, this is in my notes for VDR Taq:
+G/-A (Yasko +A/-G), AA is the majority allele, which she calls +/+, but really in conventional terms it would be -/- since it's the more common one...

It shows up in this chart that she is calling a VDR Taq of C (G) to be a -/- even though that's the minority result : http://geneticgenie.org/blog/.

GeneticGenie says he/she was reporting it the conventional way until January, when he/she decided to go with the Yasko way and flip it.

Or am I mixed up? It would not be the first time.

For VDR Bsm, I *thought* that Yasko goes along with the view of +A/-G, and in terms of 23andme reporting, the G is a C, so CC is -/- and is the result of the majority, so Yasko follows the standard line there.

---
I hope you get good care and good news at the doctor's tomorrow.

 

[Valentijn]

Oh, is the MTHFR quote I copied above about the homozygous mutations only? I was thinking it was for even the heterozygous versions.

I haven't looked too closely into it, but the effect on folate at least is only in conjunction with hetero MTHFR C677T from what I recall. I also think I read something showing little or no effect in various studies where you'd expect an effect if it was doing something to folate.

About Yasko's reporting of VDR backwards, this is in my notes for VDR Taq:
+G/-A (Yasko +A/-G), AA is the majority allele, which she calls +/+, but really in conventional terms it would be -/- since it's the more common one...

Sometimes the more common one is associated with more risk. Or it might be better to say that the rarer one is more protective! But either way you want to look at it, it's common as dirt and unlikely to be causing much of a problem. Or maybe lower D 25 (AA) is better? Not something I've looked at much!

If only Yasko could be bothered to cite some actual RESEARCH, we could spend a lot less time trying to figure out what she's suggesting.

 

[Jeri Lynn WI]

Valentijn, could you please look (again) at my Yasko results and notate??? I have no scientific training whatsoever and the more I've researched and the more tests I have (UAA/UEE's recently), the more overwhelmed I become.

HOMOZYGOUS:
CBS/C699T
MAO A/R297R
VDR/Taq and Fok



HETEROZYGOUS:
ACAT/1-02
MTRR/A66G
MTRR/11

CBS/A360A
SHMT/C1420T
NOS/D298E

Since I last posted, I've been working on treating the H. Pylori and helping my struggling adrenals with a local herbalist/nutritionist, so I'm already off the Yasko reservation, I guess, before I've even started with the GABA supps. I did the urine tests but this naturopathic-type practitioner was puzzled by why Yasko uses them, as she doesn't feel they give a true picture of what's going on. She likes the Ion Transport test by Metametrix. Any thoughts about that, too??

Thank you, Valentijn!!!

 

[Valentijn]

HOMOZYGOUS:
CBS/C699T
MAO A/R297R
VDR/Taq and Fok

CBS C699T is not the catastrophe that it's made out to be by Yasko and Heartfixer. Yes, it has an impact, but it's a rather small one. It results in lower homocysteine, which I'd consider to be a good thing. Due to it being a rather mild upregulation, I doubt it causes the sulfur or ammonia issues that are often discussed. So overall, you probably have the better version.

MAOA R297R (TT) is also one I'd hesitate to call a risk. All versions of it are quite common, and associated with different minor risks of mental disorders. With the TT you have the slower version, which means your catecholamines (dopamine, norepinephrine, epinephrine, and serotonin) aren't broken down as quickly as they are for the GG folks. At most this means that you might not enjoy supplementing catecholamine precursors.

The VDR Taq AA means slightly lower levels of D 25. I haven't looked into whether or not this is a good thing It sounds like Fok-1 TT does the same thing. So with multiple SNPs involved there, you might have some issues with Vitamin D and substances downstream. The ION panel would help with confirming that, I think. But VDR might also lead into catecholamine formation, so doing something to correct VDR problems might have the side-effect of increasing catecholamines too much.

HETEROZYGOUS:
ACAT/1-02
MTRR/A66G
MTRR/11
CBS/A360A
SHMT/C1420T
NOS/D298E

MTRR A66G GG results in increased homocysteine and possibly decreased BH4. BH4 is another one involved in catecholamine production, so again, a good idea to go carefully if messing around with it. Though with the heterozygous version, it probably has little or even no impact. I haven't been able to find any research at all showing that MTRR A664A (11) is relevant at all.

SHMT1 C1420T AA increases the effect of MTHFR C677T. But you don't have AA, and you don't have MTHFR C677T, so it's probably not an issue.

NOS3 D298E is definitely relevant even when heterozygous, and comes with some health risks. I haven't look into it much (since most people here are doing 23andMe, which doesn't list it), but it controls the production of nitric oxide. Heartfixer says more is better, and BH4 might help it out.

SUMMARY
So basically your actual methylation doesn't seem to be problematic, but you have multiple issues pertaining to catecholamine formation and breakdown. Things might be balancing out, since you could be slow both in producing and breaking down catecholamines, and doing things which effect catecholamine production (methylB12, BH4 production, vitamin D) should probably be approached with some caution.

There might be an ammonia problem due to the CBS and NOS3. I think there are actual blood tests for ammonia if you're worried about it. But dealing with nitric oxide production is probably somewhat important, due to the increased cardiovascular risks associated with that. Heartfixer recommends aggressive antioxidant supplementation, which seems pretty practical. They also suggest vitamin C and methylfolate, which also might help - though I'd stay away from anything higher than a normal dose of the methylfolate.

I did the urine tests but this naturopathic-type practitioner was puzzled by why Yasko uses them, as she doesn't feel they give a true picture of what's going on. She likes the Ion Transport test by Metametrix. Any thoughts about that, too??

Yeah, the test strips are designed for use in testing drinking and industrial water I think, so it's hard to say how useful they are for diagnosing whether there's a problem or not. Though they might be good for keeping track of changes.

It looks like a pretty useful test. It probably won't give you "The Answer" to find a cure, but it can help in showing were some of the little problems are, and maybe give you an idea of what sort of more focused testing you want to conduct. If it's not going to bankrupt you, I think that sort of testing is a really good idea.

 

[Jeri Lynn WI]

Valentijn, thank you for your prompt and really helpful response!!! Can I ask, to be perfectly clear about this: you DO NOT believe I should jump in to the Yasko Protocol 100% even given my genetics???

Do you believe I would benefit from having the Methylation Pathway test recommended by Rich Vank here (r.i.p.
and which is now offered w/out prescription through Ben Lynch's site???

Am I OK in treating my gut issues incl. H.Pylori right away even though people at the Yasko Nutrigenomics Forum say I should wait until I do Step 1, which is glutamate balance??? Same thing with my thyroid/adrenal issues???

Would I gain more useful genetic info if I also did the 23andme????

Thanks again, V.!!!

Jeri

 

[Valentijn]

Valentijn, thank you for your prompt and really helpful response!!! Can I ask, to be perfectly clear about this: you DO NOT believe I should jump in to the Yasko Protocol 100% even given my genetics???

Much of the basis for use of the Yasko Protocol (the SNPs she tests) is faulty, so I think it's probably an immense waste of money to buy her special products. There probably are vitamins and other supplements that can help you somewhat, but it seems likely that you can get them easier and cheaper elsewhere.

Do you believe I would benefit from having the Methylation Pathway test recommended by Rich Vank here (r.i.p. and which is now offered w/out prescription through Ben Lynch's site???

I think it would be of some use, but not of a lot of use, if that makes any sense. It might help you to get a clearer picture of what's going on, but then again you can try Richvank's protocol without getting the test and just see if it helps. It some cases it makes sense financially to order a test instead of spending hundreds of dollars on special supplements, but in the case of the simplified methylation protocol you can do the most basic aspects (methylfolate, hydroxyB12) cheaply and easily. The test might be good for testing progress or verifying a problem, but I don't think it's essential - more a matter of how much information you want and how much you can afford to spend to get it.

Am I OK in treating my gut issues incl. H.Pylori right away even though people at the Yasko Nutrigenomics Forum say I should wait until I do Step 1, which is glutamate balance??? Same thing with my thyroid/adrenal issues???

Unless a licensed medical doctor says otherwise (Yasko and her followers are not MDs), I'd think it makes more sense to treat a known harmful (and confirmed?) medical condition first and foremost. Also her "step 1" seems rather complicated and excessive - really the entire process seems like a great way to draw out getting to a "cure", so people invest as much money as possible while taking a very very long to see if it works or not.

Would I gain more useful genetic info if I also did the 23andme????

Probably. There are results generators other than the geneticgenie Yasko methylation one, and I'm working on getting some hopefully ME/CFS-relevant ones together - based on actual research and with citations attached.

Something else some of us have been doing with 23andMe results is running them through a rare allele program and compiling and comparing the results in this thread: http://forums.phoenixrising.me/index.php?threads/rare-allele-data.23978/

23andMe also lists known risk factors you have for some diseases - I found out that I have one copy of an allele that can cause elevated iron that way. There are also other sites that process 23andMe results and list some disease risks/associations.

 

[Jeri Lynn WI]

Thank you again, Valentijn!! I inclined myself towards a bit of skepticism about the entire Yasko Protocol, but let me play devils' advocate for a moment.

Firstly, I would presume someone like the Heartfixer doc (Roberts??) is able to assess the Yasko approach scientifically, and he seems to agree with it. If it is indeed based on flawed research, why would he validate it???

Secondly, I did find the Yasko test eerily accurate when looked at in light of my parents' history: various types of heart disease/malfunction, stroke, hypothyroidism, vascular issues incl. dementia. Isn't that CBS defect partly responsible for such awful diseases???

Thirdly, my known allergies (based on an ELISA) include things like onions and sulfites (used at salad bars, for example.) That sure seemed to validate the idea of a CBS defect.

I guess what I'd like to do is incorporate some of the ideas she has as well as get that ION Transport test through my sort-of naturopath and deal with what it finds. But e.g. at the Yasko forum someone told me iodine competes with lithium, so taking the Iodine Synergy product I was given could make low lithium levels worse. I do have longstanding depression and anxiety issues; I haven't done an HMT but my lithium on the UEE was.023 ug/mg, 50th percentile.

So I guess I'm afraid TO follow the Protocol blindly and unquestioningly, but I'm also afraid NOT to, in a way. Do you think I can improve my health by treating things that come up on the ION test as well as my obvious heath issues PLUS incorporate at least some of her ideas??? For example, I have the idea the Phos Serine or her PS/PE/PC complex would be beneficial, given my heath issues, but it's part of the "short cut" so wouldn't it trigger detox???

 

[Valentijn]

Firstly, I would presume someone like the Heartfixer doc (Roberts??) is able to assess the Yasko approach scientifically, and he seems to agree with it. If it is indeed based on flawed research, why would he validate it???

He doesn't really discuss some of the Yasko mutations, and others just get a brief discussion at the end. For BHMT, for example, he doesn't discuss the individual SNPs tested, but discusses what the gene does instead, which glosses over BHMT-08 being the only relevant one. And some of his statements are just as glaringly wrong as Yasko's, such as "CBS is operating at up to ten times its normal rate." So it seems like he's relying on what Yasko says without bothering to read the actual research, and when there is no evidence about the SNP, relying on vague statements about the gene without explicitly tying the SNP and a change in gene function together.

I also have doubts about having methylation treated by a cardiologist who focuses on fad diets and magnetic treatments to accelerate healing (?!?). At least he is a real MD from a real school, but it's quite apparent from his site that he does not verify that the information about the SNPs is accurate.

Secondly, I did find the Yasko test eerily accurate when looked at in light of my parents' history: various types of heart disease/malfunction, stroke, hypothyroidism, vascular issues incl. dementia. Isn't that CBS defect partly responsible for such awful diseases???

Maybe, albeit to a small extent. But the 10x upregulation claim is based on a study of the SNP involving a bioengineered yeast specifically designed to emphasize the effects of the SNP to determine if it has an effect on the gene. It does have an effect, but the effect it has on the mutant lab yeast cannot be extrapolated from to conclude that it effects the CBS gene in humans to anywhere near the same extent!

Thirdly, my known allergies (based on an ELISA) include things like onions and sulfites (used at salad bars, for example.) That sure seemed to validate the idea of a CBS defect.

Or a zillion other things could be causing a reaction to sulfites. It's possible you have a mutation on a different CBS SNP which is causing problems, or more likely there's an issue with a different gene or biological process gone awry.

So I guess I'm afraid TO follow the Protocol blindly and unquestioningly, but I'm also afraid NOT to, in a way. Do you think I can improve my health by treating things that come up on the ION test as well as my obvious heath issues PLUS incorporate at least some of her ideas??? For example, I have the idea the Phos Serine or her PS/PE/PC complex would be beneficial, given my heath issues, but it's part of the "short cut" so wouldn't it trigger detox???

I think the exaggerations about the SNPs and the "OMG I have 5 red genes" is creating an atmosphere of mild hysteria, so I certainly understand where that fear is coming from. Hence I think it's extremely important to read the research and see what the actual impact of the SNPs are, and to understand when a variation is and is not particularly relevant. If someone thinks information and independent verification are a bad or dangerous thing, then it looks an awful lot like a cult. I think the best way to go is to educate yourself as best your can.

I think ION and SNP results can definitely be used in conjunction. To start with, they can help verify how much of an effect those SNP variations are having. And while the effect of the SNPs is often badly exaggerated, the basic description of the effect of the genes seems pretty accurate.

 

[Bluebell]

Post by Jeri Lynn WI

+

...I think it's extremely important to read the research and see what the actual impact of the SNPs are, and to understand when a variation is and is not particularly relevant.

If someone thinks information and independent verification are a bad or dangerous thing, then it looks an awful lot like a cult.

I think the best way to go is to educate yourself as best your can.

Jeri Lynn WI, I agree so much with Valentijn on the points from her that I've quoted here.

I believe that Valentijn will not be offended if I also say that her advice and information can be helpful and are based on a great deal of careful study, but she is a lawyer by training, not a medical professional of any kind (as far as I am aware), so one should not rely too much on her opinions when deciding what to do for one's own health.

She comes at the topic with her own mindset and health situation (as we all do), and because she has comparatively few of "these types" of mutations, and because she has not herself tried any of the Rich/Yasko/Freddd methylation protocols, the advice that she (kindly and generously!) offers can be added to that from other sources, but is not complete in itself.

----
Rich van Konynenburg said that the methylation pathways panel was the number one thing he would do, and that it was highly recommended before starting a methylation trial, if the cost were affordable for the patient. He also was in favor of some other, more expensive tests like the Nutreval and so on, and described why. If you have the budget for some of these tests, I would suggest reading through his main writings to see what he recommended, and the reasons he gave (he always explained his thinking clearly). [There are links to some of his most helpful summaries, threads, documents, and videos in my "methylation information links" thread, which can be found below my signature line here-->]

Rich also wrote that for adults who don't have autism, he felt that starting "low and slow" with his basic protocol was relatively safe and relatively applicable to many people's situations, and it could be tailored if the basic plan didn't work after a couple of months.

---
Not that you asked for anyone else's opinion -- but I agree with Valentijn that doing the 23andme test provides a lot of great info - even beyond the methylation genetic results - and is well worth doing for $99. You'll have to wait about 2 months for the results though.

I also agree with her that taking care of your H Pylori problem would be smart to do asap. You need to have your digestive system working well before getting into methylation. The patients who were studied in Rich's methylation protocol experiment had already seen a doctor and had worked on other health problems that they had, before starting this.

For what it's worth, I have seen on the internet where others say that they agree with your naturopath about the lack of utility of the urine strips for this use.

I guess I'm afraid TO follow the Protocol blindly and unquestioningly, but I'm also afraid NOT to, in a way. Do you think I can improve my health by treating things that come up on the ION test as well as my obvious heath issues PLUS incorporate at least some of her ideas???

If your "sort-of" naturopath is open-minded about this stuff, maybe it would be best to work in tandem with her (or with a different local healthcare provider you trust) to forge a middle way, so you can benefit from her general training and experience in health, added to your own extensive knowledge and continuing research in this area, and of course your physical responses from trying different things.

You could also consider, if you wanted to, that some of the practitioners in this area offer phone or Skype consultations, either with a distant patient directly, with the patient's local health provider one-on-one, or with them both, to guide them through the process. It might be something you could try for a half-hour consultation, let's say, to give you and your naturopath a grounding in what's involved and what the expert's personal recommendations would be for your genetic results (whether or not you chose to follow all the recommendations later would be your call, of course).

I am not sure if Ben Lynch is accepting patients or booking long-distance advice sessions. I think that Rich van Konynenburg's research partner, Dr. Neil Nathan, might be. I think that in recent months some naturopaths have hooked up with Sterling Hill to offer some of this via her website.

 

[Bluebell]

Sometimes the more common one is associated with more risk. Or it might be better to say that the rarer one is more protective!

But either way you want to look at it, it's common as dirt and unlikely to be causing much of a problem.

Or maybe lower D 25 (AA) is better? Not something I've looked at much!

I understand the idea that a minority version might be more protective, at least in some people in some environments.

Yet, I think that having the VDR Taq +/+ in Yasko's terminology (it would be "normal" or -/- in conventional terminology) is indeed protective, or less problematic, in certain/most situations for certain/most people, even according to Yasko, and I did read a little about this in one of her books or handbooks (I ingested so much so quickly that I only have dim memories of what I've read, so that's all I remember).

Having the VDR Taq as AA ("+/+") definitely makes some of *my* other mutations less of a problem, according to Heartfixer and Yasko. Maybe nature throws these mutations together sometimes, to help us mutants out a little.

In fact, I do not think I ever saw a mention by Yasko or Heartfixer of where the "+/+" VDR Taq made my situation worse. (Although, I've hardly researched their takes on my genetic results yet because I put it on the back burner after getting my unexpected blood test results, which opened up a few other cans of worms that I need to see to first.)

I've read in some threads that it's a puzzle why she designates the VDR Taq this way, because it isn't logical, but they say she doesn't explain it. Then there was the controversy with Geneticgenie, which eventually capitulated to the popular demand to mirror Yasko perfectly and switch the notation for VDR Taq around.

---
It's all pretty complicated and I know very little.

I'm not even totally sure what "addressing" one's, say, ammonia or COMT is about.

So I imagine myself, as a male version of me, in a bowler hat and cane, in front of the Bank of England, in a garishly-colored 1950s film, with a doubler-decker bus careering around the corner behind me, saying, "Good day, Mr. Ammonia", "Looking well, Miss CBS" (wink wink), "See you down the pub, BMHT old chum".