A gene testing challange

[Freddd]

There are a lot of people here who would like to see me have my genes tested. I have put all sorts of reactions to various nutrients out there. I have healed and recovered from FMS, CFS and congestive heart failure. You could probably throw ME in to that mix too except I never had the diagnosis since it is not used in the USA.

The challenge is this. You all know what has worked for me if you have read my posts. Based on what worked, according to the interpretations of the gene tests, what SNPs should be of what forms for all these things to work. I would like to see some predictions of how will they come out, individual opinions or a group effort or both. Work it backwards. Reverse engineer the thinking. I've been putting my hypothesis out there for 11 years as it has developed and expanded.

So what polymorphisms "should" I have to have the reactions and responses I do? A lot of people here are betting their life on the interpretations. Let's see if all those gene tests would have guided me to what I have found pragmatically to work or would they have gotten it wrong and made me sicker or left me sick?

 

[PeterPositive]

I find it unlikely that this will work
Maybe some people take SNPs too literally, but we should know that those polymorphisms are just predisposing factors not illness-switches.

I initially have made the same mistakes.. once I knew I had the mhtfr 677 double mutation and a bunch of other B12-related ones, I jumped to too quick conclusions.

Plus the science behind these polymorphisms is so young that we're likely missing a ton of other stuff. And it's too simplistic to reduce a complex, multi-factorial illness such as ME / CFS to a bunch of genetic "errors". If it was that simple we wouldn't be here keeping each other's company, and exchanging lab tests and experiences...

Intriguing post, though
Cheers

 

[Freddd]

I find it unlikely that this will work
Maybe some people take SNPs too literally, but we should know that those polymorphisms are just predisposing factors not illness-switches.

I initially have made the same mistakes.. once I knew I had the mhtfr 677 double mutation and a bunch of other B12-related ones, I jumped to too quick conclusions.

Plus the science behind these polymorphisms is so young that we're likely missing a ton of other stuff. And it's too simplistic to reduce a complex, multi-factorial illness such as ME / CFS to a bunch of genetic "errors". If it was that simple we wouldn't be here keeping each other's company, and exchanging lab tests and experiences...

Intriguing post, though
Cheers

I'm hoping it inspires some good discussion. Lists of things that shouldn't be there like whatever it is that people interpret about what forms of b12 and folates and methylation considerations from them would be as interesting as things that "should be there".

I'm interested in finding what genes control how much B12 gets into and is retained in the cerebral spinal fluid and The ones that cause so many of us to have slow potassium replenishment from tissue to serum, the need of a specific form of carnitine as a vitamin as well as the more popular ones. These perhaps could turn out to be test targets for defining what exactly we have. I wouldn't be surprised if hundreds of genes are involved.

There is an awful lot of absolutist sounding advice from some persons interpreting these tests. The results of treating to those tests (and a lot of other tests) are much less than would be desired and I really don't trust because they are influenced by the assumptions induced by decades of folic acid and CyCbl research and in the food supply. BUT, I am interested in how it turns out and I want to see how these ideas are applied. This whole idea of reverse engineering is important because that is what has to be done to cure these illnesses.

The logic needs to be debugged. Data needs debugging too.

 

[Valentijn]

I find it unlikely that this will work
Maybe some people take SNPs too literally, but we should know that those polymorphisms are just predisposing factors not illness-switches.

Some have no impact, some are predisposing factors, some have a very minor impact on gene function, some have a significant impact on gene function, and some are exactly illness-switches.

The problems arise when the various categories get confused with each other. Yasko, for example, makes a big deal out of many SNPs which have no impact, or are merely predisposing, or have a minor impact. And then SNPs which really do have a significant impact (MTHFR C677T, MTRR A66G) are added to the mix.

 

[PeterPositive]

I'm hoping it inspires some good discussion. Lists of things that shouldn't be there like whatever it is that people interpret about what forms of b12 and folates and methylation considerations from them would be as interesting as things that "should be there".

I'm interested in finding what genes control how much B12 gets into and is retained in the cerebral spinal fluid and The ones that cause so many of us to have slow potassium replenishment from tissue to serum, the need of a specific form of carnitine as a vitamin as well as the more popular ones. These perhaps could turn out to be test targets for defining what exactly we have. I wouldn't be surprised if hundreds of genes are involved.

There is an awful lot of absolutist sounding advice from some persons interpreting these tests. The results of treating to those tests (and a lot of other tests) are much less than would be desired and I really don't trust because they are influenced by the assumptions induced by decades of folic acid and CyCbl research and in the food supply. BUT, I am interested in how it turns out and I want to see how these ideas are applied. This whole idea of reverse engineering is important because that is what has to be done to cure these illnesses.

The logic needs to be debugged. Data needs debugging too.

So are you going to do a gene test and see how it matches the various theories around here?

 

[Valentijn]

@Freddd - because you have extremely rare issues regarding vegetables and folinic acid, if I recall corrently, the program at http://sourceforge.net/projects/analyzemygenes/ might turn up something relevant. Basically it's a small download which filters out the very rare results from your 23andMe file, which can then be looked up online to see if it's on a relevant gene and/or known to be a pathogenic mutation.

The genes I have listed as being pretty closely involved with B12 and folate are:
RFC
DHFR
TYMS
MTHFR
SHMT1
SHMT2
MTR
MTRR
MTHFD1
MTHFD2
MTHFD1L
MTHFD2L
MTHFD1P1
GART
GGH
FPGS
ATIC
FOLR1
FOLR2
FOLR3
FOLR4
FOLH1
FOLH1B
SLC46A1
SLC19A1
SLC25A32
CUBN
TCN1
TCN2
GIF
ABCD4
MUT
MMAA
MMAB
MMACHC
MMADHC
LMBRD1
LMBRD2

Once you have a 23andMe account and data, you can find your genotypes for the SNPs which they test on those genes at https://www.23andme.com/you/explorer/ . Then you can usually find data regarding rarity and whether each SNP is a missense and/or pathogenic mutation at www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=

 

[taniaaust1]

I find it unlikely that this will work
Maybe some people take SNPs too literally, but we should know that those polymorphisms are just predisposing factors not illness-switches.

I initially have made the same mistakes.. once I knew I had the mhtfr 677 double mutation and a bunch of other B12-related ones, I jumped to too quick conclusions.

Plus the science behind these polymorphisms is so young that we're likely missing a ton of other stuff. And it's too simplistic to reduce a complex, multi-factorial illness such as ME / CFS to a bunch of genetic "errors". If it was that simple we wouldn't be here keeping each other's company, and exchanging lab tests and experiences...

Intriguing post, though
Cheers

I actually knew I had a CBS gene mutations from my history and things (issues with certain foods) and with testing my thoughts proved to be correct. My doctor also knew I had MTHFR mutation (due to my homocysteine levels before I even was tested, he was correct.

So Im going to say that if one really knows what one is looking for, one may pick these up before testing.

 

[taniaaust1]

I have healed and recovered from FMS, CFS and congestive heart failure.

My guess is a double copy of MTHFR mutation just cause you had congestive heart failure and the fact youve managed to recover from it with methylation (I assume you were taking the same kinds of things used for MTHFR mutation?)

This is still a wild guess based on those things, but I'd be more sure if you have had a homoecysteine test and shared with me what your results were (as some results even in normal range can indicate MTHFR mutation).

Have you had any blood tests which showed things clotting slightly faster then they should?

 

[taniaaust1]

@Freddd - because you have extremely rare issues regarding vegetables

To what vegatables does FREDD react?

 

[brenda]

Freddd reacts to too many vegetables that are high in folate, like me. It was the reason I had to quit raw vegan.

 

[Freddd]

My guess is a double copy of MTHFR mutation just cause you had congestive heart failure and the fact youve managed to recover from it with methylation (I assume you were taking the same kinds of things used for MTHFR mutation?)

This is still a wild guess based on those things, but I'd be more sure if you have had a homoecysteine test and shared with me what your results were (as some results even in normal range can indicate MTHFR mutation).

Have you had any blood tests which showed things clotting slightly faster then they should?

Hi Tania,

The CHF had two aspects. I had immediate onset edema as soon as the folate "flips" to insufficiency followed by epithelial lesions and inflammation.. The second factor that triggered actual healing was the AdoCbl/LCF. Suddenly when I started that muscles that had been atrophying for 20+ years. The LCF appears to cause first a proliferation of mitochondria and then growth of cells. My aerobic capacity increased very quickly after being stuck for more than a year with no improvement. The muscle pain changed within days from acutely sore to "post exercise" feeling and improved from there very quickly. My heart appeared to strengthen at the same time as my muscles and the second half of the edema poured off my body, 45 pounds of water in a couple of months, and kept going as 40-50 pounds of fat went away too. I was taking the Deadlock Quartet. Carnitine causes production of osteoblasts, neuroblasts and likely other cells when conditions are reached.

I have never had a homocysteine test that the doc discussed with me. It was always "normal", probably just barely along with the rest of my blood measures. I was asked by multiple docs, including ones who removed me from their practice if I had any problems with delayed clotting of blood. I was also accused of being an alcoholic and lying to the docs. When asked about alcohol use at that time, I would start to answer "About a 6 pack per ..." and the doc would break in and say "per day" and I would say "No, per year". Then after a discussion about alcohol which was a total distraction and blind alley I would be kicked out of the practice for persistent lying despite the "evidence".

 

[shah78]

Do we win a prize for the closest? You are in rare form Fred since your return. For the sake of controversy I'm hoping for many COMT ++ . (like myself). with the attached warning from Mount Olympus."Thou shalt avoid methyl forms of b12" (Yeah sure.) "Use only Hydoxy and Adenesyl forms." ......This experiment is like Nixon going to China! Thanks for keeping us entertained. You are indeed "THE MAIN MAN OF METHYLATION".

 

[Freddd]

Do we win a prize for the closest? You are in rare form Fred since your return. For the sake of controversy I'm hoping for many COMT ++ . (like myself). with the attached warning from Mount Olympus."Thou shalt avoid methy forms of b12" (Yeah sure.) "Use only Hydoxy and Adenesyl forms." ......This experiment is like Nixon going to China! Thanks for keeping us entertained. You are indeed "THE MAIN MAN OF METHYLATION".

Hi Shah,

Do we win a prize for the closest?

I'm good for a lunch or two in whatever locale I am in, usually Salt Lake City or Denver and surrounding areas. And maybe for most interesting or best explanations or whatever, and especially, who is around to go to lunch with.

 

[whodathunkit]

@Freddd: I suggest a free 30ml bottle of 1mg/ml injectable mB12 (or hydroxy, their choice), and 30 syringes, as first prize.

I echo Peter Positive: are you planning to get your genes tested? Or just curious to see what people come up with, if they're interested?

 

[shah78]

It's been twenty six hours since Nixon declared his intension to go the China, no.... its been twenty six hours since Neil Armstrong stepped onto the surface of the Moon,no.... it's been twenty six hours since Freddd said he'd take (or already taken) a 23 and me test. Where is the outpouring of opinion?This is the biggest PR "STORY" since........ "EVER"! Get your guesses,theories, in! What are you waiting for? This is CFS history. This is like being on the mound with Curt Schilling and the bloody sock!

 

[taniaaust1]

I have never had a homocysteine test that the doc discussed with me. It was always "normal", probably just barely along with the rest of my blood measures. I was asked by multiple docs, including ones who removed me from their practice if I had any problems with delayed clotting of blood. I was also accused of being an alcoholic and lying to the docs. When asked about alcohol use at that time, I would start to answer "About a 6 pack per ..." and the doc would break in and say "per day" and I would say "No, per year". Then after a discussion about alcohol which was a total distraction and blind alley I would be kicked out of the practice for persistent lying despite the "evidence".

Typical bad doctors who prefer to think we lie then take a real good look at us.

That "normal" with the homocysteine test doesnt mean much as far as MTHFR goes as lots of us with it have homocysteine in the normal range. Thing is it can be usually told from a normal test result if one goes by the level. (I didnt even see my test result as being a high normal but my specialist immediaely went "im sure you have MTHFR from that result", he then actually treat me for MTHFR then without a MTHFR test as he was so sure. I thou asked then for the MTHFR test so got that as I didnt believe him.

Pity you dont know your test results. (Also who knows what things the doctors have not told you. A couple of my past doctors told me my results were normal but when I asked for tests years later, I saw many things out of range including severe hypoglycemia on my tests that I hadnt been told about, seems many doctors ignore that as all they are concerned about is diabetes).

 

[Freddd]

Typical bad doctors who prefer to think we lie then take a real good look at us.

That "normal" with the homocysteine test doesnt mean much as far as MTHFR goes as lots of us with it have homocysteine in the normal range. Thing is it can be usually told from a normal test result if one goes by the level. (I didnt even see my test result as being a high normal but my specialist immediaely went "im sure you have MTHFR from that result", he then actually treat me for MTHFR then without a MTHFR test as he was so sure. I thou asked then for the MTHFR test so got that as I didnt believe him.

Pity you dont know your test results. (Also who knows what things the doctors have not told you. A couple of my past doctors told me my results were normal but when I asked for tests years later, I saw many things out of range including severe hypoglycemia on my tests that I hadnt been told about, seems many doctors ignore that as all they are concerned about is diabetes).

I started with a new doc, an internist about May 18th, 2003. It was 3 days later I started MeCbl and everything changed. When he saw me 3 weeks later he said that the tests were irrelevant now and ordered a whole new set of tests. I never did see or discuss those. As he is still my doctor I could ask for them when I see him in in a couple of months. I've asked for my records from one earlier doc I was with when I crashed, and they are all in "long term storage" and time consuming and expensive to retrieve. Another doctor moved to Montana and is probably retired. The rest got rid of me or were one appointment interviews or specialists. Some of the interviews were very short.

I had one of those things occur where my doc said "normal" for something that had been alerted all my life, MCV. It was about 7 years ago. He said "Good news", your MCV came back normal this time". I asked the number. It was 99.8, unchanged. What was changed was the upper limit which was now > 100.0, previously > 96 for alert. Some labs have gone as high as 102. The abnormal has become normal. I always get a copy now but I get a lot less testing now, mostly checking on my response to prescriptions

Obviously there was a pattern on my CBC that read "alcoholism" even if all in range except MCV/MCH, and they were "borderline" while I was crashed. It must have been plain enough for quite a few docs to notice and make an issue of it.

 

[whodathunkit]

I had one of those things occur where my doc said "normal" for something that had been alerted all my life, MCV. It was about 7 years ago. He said "Good news", your MCV came back normal this time". I asked the number. It was 99.8, unchanged. What was changed was the upper limit which was now > 100.0, previously > 96 for alert. Some labs have gone as high as 102. The abnormal has become normal.

Creeping abnormalcy. Hell of a thing. *shudder*

 

[skwag]

Hey Freddd,

Hope all is well. Anyway, I'm going to take a shot at this. I'm basing all my guesses off @caledonia 's excellent SNP interpretation guide along with what I know about my own SNPs and the similarities I share with you. I'll only guess on the SNPs that genetic genie outputs from 23andme results.

ACAT1-02 -/-

CBS C699T, A360A -/-
BHMT-02, BHMT-08 -/-
You might have a couple -/+ in there, but I don't remember you describing CBS type symptoms, so no big problems there.

MTHFR 677T, MTHFR 03 P39P -/-
It's a bold guess, I know!

MTHFR A1298C +/+
Without high(?) methylfolate supplementation this causes a BH4 deficiency, which produces a bunch of oxidative damage along with a serotonin and dopamine shortfall.

MTR A2756G -/+
Have no idea on this one really

MTRR ( all 4 of them) +/+
According to caledonia, these mutations downregulate MB12 recycling. If anybody has them all, it is you.

COMT ( all 3 of them) -/-
Probably one or two +/- in there, but if caledonia's warning about excessive methyl groups is true, I think you are mostly ok here.

MAO A R297R + or +/+
This is the warrior SNP, no?

VDR BSM -/-
VDR Taq +/+

AHCY-01, AHCY-19 -/-


So, do you have your results yet?

 

[Valentijn]

MAO A R297R + or +/+
This is the warrior SNP, no?

No. It's an SNP which alters how quickly certain neurotransmitters are broken down. Anything beyond that is a rather gross (and often insulting) mischaracterization.