Rich, do you have to inherited snps from both parents to have the problems with glu?

[anniekim]

Hi rich,

I was just wondering whether you have to have inherited a snp that interferes with recycling or making glutathione from both parents to cause problems or just one parent is suffice? Many thanks

 

[richvank]

Hi rich,

I was just wondering whether you have to have inherited a snp that interferes with recycling or making glutathione from both parents to cause problems or just one parent is suffice? Many thanks

Hi, anniekim.

I don't know, and wish I did. The SNPs in the glutathione system have not been studied in ME/CFS, as far as I know. I have encouraged some of the genomic researchers to look at this, but I don't think they have yet. Dr. Shoemaker may look into the gene expression of the enzymes in the glutathione system in his patients, and that may give clues about SNPs. Have to wait and see.

Best regards,

Rich

 

[Vegas]

Hi, anniekim.

I don't know, and wish I did. The SNPs in the glutathione system have not been studied in ME/CFS, as far as I know. I have encouraged some of the genomic researchers to look at this, but I don't think they have yet. Dr. Shoemaker may look into the gene expression of the enzymes in the glutathione system in his patients, and that may give clues about SNPs. Have to wait and see.

Best regards,

Rich

Rich, I wonder if this would be relevant to a subset of ME/CFS patients, like myself. This is a study that was just published last month:

Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).

As you may recall stimulating the GST enzymes has been quite helpful for me...zinc, selenium, polyphenols. I realize these have multiple physiological activities, but there really haven't been too many things to help...so I thought this was significant.

 

[globalpilot]

Very Interesting. Here is the abstract.

http://www.ncbi.nlm.nih.gov/pubmed/21967774

Rich, I wonder if this would be relevant to a subset of ME/CFS patients, like myself. This is a study that was just published last month:

Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).

As you may recall stimulating the GST enzymes has been quite helpful for me...zinc, selenium, polyphenols. I realize these have multiple physiological activities, but there really haven't been too many things to help...so I thought this was significant.

 

[anniekim]

Hi, anniekim.

I don't know, and wish I did. The SNPs in the glutathione system have not been studied in ME/CFS, as far as I know. I have encouraged some of the genomic researchers to look at this, but I don't think they have yet. Dr. Shoemaker may look into the gene expression of the enzymes in the glutathione system in his patients, and that may give clues about SNPs. Have to wait and see.

Hi Rich,

Best regards,

Rich

Thanks for your reply. I'm sorry I am getting a bit confused now. You have written that to get an isolated case of CFS/ME one has to have inherited some genetic polymorphisms from your parents. I'm taking from that you do know which snps indicate whether a person may have a problem with making gluthathione or recycling gluthathione? So it's just at this stage you don't know whether having two or one inherited snps makes a further difference?

Also I'm sure you have written it elsewhere but am fading so not up to trawling through the posts so can I ask what is the test that shows the relevant snps?

Many thanks

 

[richvank]

Hi, Vegas and globalpilot.

Thanks for posting this. It's good to see that mercury detox is getting more attention. I look forward to getting a copy of the complete paper. Yes, I do think this is relevant to some people who have ME/CFS.

The two GSTP1 SNPs that are cited in this abstract are characterized on the Genovations Detoxigenomic profile, and some people who have ME/CFS do have one or the other of these SNPs. I haven't seen data on the others in PWMEs, but they may be covered by 23andme.com, so in the future, people may be able to get these data on themselves. I think that as time goes by we will be able to build our understanding of which genomic polymorphisms we should look at for an individual PWME, to be better able to understand each case and what should be done about it. Dr. Amy Yasko has pioneered this type of approach, and it can get pretty complicated, but it may be needed, particularly in some cases. If there is a high body burden of mercury, it can be blocking important enzymes, and this can prevent recovery of some people on the methylation treatment. We had an example of that in our clinical study (Dr. Nathan and I). I discussed that case at the end of the seminar I presented in Sweden in October. It was an 84-year-old lady, and she did not improve on the methylation treatment until she had chelation to remove heavy metals. Then she improved rapidly, and was able to travel to Paris with her friends.

The state of the body's detoxication system is an individual thing. When toxicological studies have been done, they usually include people from the general population, and the results are averaged together. This can obscure individual differences, which can be very important to the particular individuals involved. I think that in the ME/CFS population, we are often seeing people who do not have a normal detox system, because of their particular inherited polymorphisms--the term "canaries in the coal mine" has sometimes been applied, and I think it's relevant to some PWMEs. I'm glad to see study of these SNPs and how they affect excretion of mercury.

As you may know, a few years ago in autism research is was found that some of the kids were "excretors," and some were "non-excretors" with regard to mercury in hair, and it was realized that a low hair mercury level could actually indicate that there was a higher toxic burden in the body, because it was not being excreted.

There is a subset of PWMEs who have normal glutathione levels on the methylation pathways panel, but still have a partial methylation cycle block. I've had a small amount of data that suggests that these people may have SNPs in their GST enzymes, so that even though they have enough glutathione, they are not able to use it as well as normal to conjugate heavy metals, such as mercury, because the enzymes that normally do the conjugating have genetic problems.

I'd be interested in hearing more about how you have been able to stimulate your GST enzymes. I think that could be helpful for others who have this situation.

Best regards,

Rich

 

[globalpilot]

Hi Rich and all,
Here is another similiar study (full paper):
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002267

In it, you'll see that hair mercury goes up if there is a heterozygous mutation and up further if there are 2 (except for a couple of cases).

I was thinking about low hair mercury today Rich after reading this paper so it's funny you mentioned this. The mercury they mention for those with normal genes is around 170 or so but then goes up if they conjugate glutathione more poorly. So I'm not sure anymore if low hair mercury means poor excretion. Mine was 30. I'm thinking now maybe it indicates low cysteine which is the case for me.

 

[aquariusgirl]

There's a lot of talk about mercury & lead & aluminum, but I am beginning to wonder if copper retention/toxicity isn't a problem for those of us who have KPU, or for some reason are deficient in zinc.
My understanding is that one accumulates copper if one is low in zinc & that reminds me that Peta Cohen, autism doc, found her kids "blew out copper" when she put them on a biofilm protocol.
Anyone know what a good copper chelator is?

ETA: I just checked out the other threads on copper toxicity. Interesting stuff. I guess high dose Vit C might be helpful in reducing copper load... but would prolly exacerbate glut deficiency...if I understand Rich correctly.

 

[richvank]

Thanks for your reply. I'm sorry I am getting a bit confused now. You have written that to get an isolated case of CFS/ME one has to have inherited some genetic polymorphisms from your parents. I'm taking from that you do know which snps indicate whether a person may have a problem with making gluthathione or recycling gluthathione? So it's just at this stage you don't know whether having two or one inherited snps makes a further difference?

Also I'm sure you have written it elsewhere but am fading so not up to trawling through the posts so can I ask what is the test that shows the relevant snps?

Many thanks

Hi, Anniekim.

I'm sorry if I have misled you into believing that all of this is understood and proven at this point. Unfortunately, it is not. There is still research to be done. What I have done is to develop a hypothesis to help point toward the types of research that are likely to be the most beneficial in improving our understanding of this disorder. There is quite a bit of evidence that supports the hypothesis, in my opinion, but there are still pieces that have not been tested. Nevertheless, we have used it to develop treatment, and the treatment has been significantly helpful to most who have tried it, but only a few have made what appear to be complete recoveries. There is still much to be learned.

I have inferred from published information on family studies, twin studies and the available polymorphism studies that there is a genetic component that makes people vulnerable to developing at least the sporadic cases of ME/CFS. I have inferred from the published risk factor studies, responses to my own questionnaires and the known biochemistry that glutathione depletion is what starts off the onset of ME/CFS, in response to a variety of stressors. I believe that in order for a polymorphism to be important in affecting the likelihood of onset, it must be near the beginning of the pathogenesis, in order to be accessed and to therefore make a difference. Putting all of these factors together, I have inferred that there must be relevant polymorphisms in the glutathione system that predispose a person to the development of ME/CFS. This is a hypothesis. It has not yet been tested, because the polymorphisms in the glutathione system in people who have ME/CFS have not yet been studied. I hope they will be, and have encouraged some of the genetic researchers to do so.

Best regards,

Rich

 

[Freddd]

Hi, Anniekim.

I'm sorry if I have misled you into believing that all of this is understood and proven at this point. Unfortunately, it is not. There is still research to be done. What I have done is to develop a hypothesis to help point toward the types of research that are likely to be the most beneficial in improving our understanding of this disorder. There is quite a bit of evidence that supports the hypothesis, in my opinion, but there are still pieces that have not been tested. Nevertheless, we have used it to develop treatment, and the treatment has been significantly helpful to most who have tried it, but only a few have made what appear to be complete recoveries. There is still much to be learned.

I have inferred from published information on family studies, twin studies and the available polymorphism studies that there is a genetic component that makes people vulnerable to developing at least the sporadic cases of ME/CFS. I have inferred from the published risk factor studies, responses to my own questionnaires and the known biochemistry that glutathione depletion is what starts off the onset of ME/CFS, in response to a variety of stressors. I believe that in order for a polymorphism to be important in affecting the likelihood of onset, it must be near the beginning of the pathogenesis, in order to be accessed and to therefore make a difference. Putting all of these factors together, I have inferred that there must be relevant polymorphisms in the glutathione system that predispose a person to the development of ME/CFS. This is a hypothesis. It has not yet been tested, because the polymorphisms in the glutathione system in people who have ME/CFS have not yet been studied. I hope they will be, and have encouraged some of the genetic researchers to do so.

Best regards,

Rich

Hi Rich,

I would have to agree that there are without a doubt some gentic components that affect at the very least, the handling of folate, the ability go transport cobalamin into the cerebral spinal fluid, retaining cobalamin in cerebral spinal fluid, and probably some other cobalamin metabolic errors that cause problems without being a 100% shutoff. There could be a whole lot more genetic differences that distinguishes amonst a whole grouping that appears to have at least some common causes. The question I woild like to place is what has occurred progressively in the past 50 years that has dramatically increased the incidence of CFS, FMS, ME, Alzheimer's, Autism, Parkinson's, MS, ALS, SupraNuclearPalsy and who knows what other problems as a whole. My three children all had similar folate/b12 impairments but some differences as well. Two of them were able to head off the development of CFS/FMS with mb12/adb12/methylfolate and their symptoms backed off. The other had traumatic injuries from a car accident and proceeded into FMS after intially having the symptoms back off and she was recovering again when she was killed.



We would do a lot better if a whole lot of providers didn't have belief systems that cause them to call us names and treat us badly because they don't want to believe that we can really be so sick and have so many "in-range" tests. Interpretation of tests are perhaps the key. Consider the studies on Cerefolin with NAC, they could not recoginze an induced folate deficiency when it hit some of their subjects in the face because they were giving a folate so it was "inconceivable!" (PRINCESS BRIDE). This, in connection with all the folks who are called names for having paradoxical folate deficiency, induced folate deficiency, "detox" otherwise known as "induced folate deficiency" or occasionally "low potassium"leads me to believe that folate deficiency is not something that is recognized symptomatically. Not a doc I ever went to recognized it and I've had it all my life and been to lots of doctors. The people now finding out that they have an induced or paradoxical folate deficiencies have the same experience; not a single practioner has likely ever recognized it. Believe me, it makes people sick as many are finding. If anybody has ever had a practitioner of any kind recognize these induced/paradoxical folate deficiency by symptoms and/or effectively treat it, please speak up.

 

[anniekim]

Hi, Anniekim.

I'm sorry if I have misled you into believing that all of this is understood and proven at this point. Unfortunately, it is not. There is still research to be done. What I have done is to develop a hypothesis to help point toward the types of research that are likely to be the most beneficial in improving our understanding of this disorder. There is quite a bit of evidence that supports the hypothesis, in my opinion, but there are still pieces that have not been tested. Nevertheless, we have used it to develop treatment, and the treatment has been significantly helpful to most who have tried it, but only a few have made what appear to be complete recoveries. There is still much to be learned.

I have inferred from published information on family studies, twin studies and the available polymorphism studies that there is a genetic component that makes people vulnerable to developing at least the sporadic cases of ME/CFS. I have inferred from the published risk factor studies, responses to my own questionnaires and the known biochemistry that glutathione depletion is what starts off the onset of ME/CFS, in response to a variety of stressors. I believe that in order for a polymorphism to be important in affecting the likelihood of onset, it must be near the beginning of the pathogenesis, in order to be accessed and to therefore make a difference. Putting all of these factors together, I have inferred that there must be relevant polymorphisms in the glutathione system that predispose a person to the development of ME/CFS. This is a hypothesis. It has not yet been tested, because the polymorphisms in the glutathione system in people who have ME/CFS have not yet been studied. I hope they will be, and have encouraged some of the genetic researchers to do so.

Best regards,

Rich

Hi Rich,

Don't worry you haven't misled me, just me not understanding it all. Thank you for the clarification and your hard work. May I ask though which gene tests are people doing in relation to methylation as i read about people doing gene tests? I take it these gene tests are still in the infancy and just give an overview/indication of possible problems in the methylation cycle? Many thanks

 

[richvank]

Hi Rich,

Don't worry you haven't misled me, just me not understanding it all. Thank you for the clarification and your hard work. May I ask though which gene tests are people doing in relation to methylation as i read about people doing gene tests? I take it these gene tests are still in the infancy and just give an overview/indication of possible problems in the methylation cycle? Many thanks

Hi, anniekim.

Quite a few people have had the methylation SNPs (sincgle nucleotide polymorphisms) panel offered by Dr. Amy Yasko (http://www.doctoramyyasko.com or more specifically,

http://www.holisticheal.com/comprehensive-methylation-panel-with-methylation-pathway-analysis.html).

It has 30 SNPs on it that she has selected. The basis for her selection is that these SNPs are associated with the methylation cycle and related pathways, and that they assist in deciding about treatment for the individual. She uses this panel primarily for treating cases of autism, but it has also been used in ME/CFS and in several of the adult neurological disorders. I initially encouraged people to try the full Yasko treatment for ME/CFS, and some people have done so. However, it is very complex and fairly expensive, so that it was not feasible for many PWMEs to use. Therefore, in early 2007, I proposed a simplified version of it. I have also encouraged people to run the Health Diagnostics and Research Institute methylation pathways panel to determine whether there is a partial methylation cycle block and glutathione depletion, and to monitor the progress of treatment. Dr. Yasko does not use this panel, but I find it to be more direct than inferring the status of these parts of the metabolism from the set of tests that she uses, including the SNPs panel. I have no objection to using the tests she recommends, and in fact, if a person has the resources to do so, they can be very helpful. But for someone who is looking for a more streamlined approach at lower cost, I favor running the methylation pathways panel, and if it shows these problems, then to try the simplified treatment approach.

In addition to the simplified methylation protocol that I have proposed, there are now several other methylation-type treatments in use by various people. Freddd, on these forums, encourages the use of a somewhat different protocol that has helped him and several others. The simplified treatment will not work for him, and apparently not for some others, either. The reasons appear to be genetic, but we have not completely nailed them down yet. I think they involve the MTHFS and the MMACHC genes. There are also other methylation-type protocols in use by various physicians. All of them have in common that they include a fairly high dose of B12, either sublingual or injected, and a more normal dosage of folate, most of them using the active forms of folate, which are 5L-methyl tetrahydrofolate and folinic acid. Some people appear not to be able to tolerate folinic acid, and some do not tolerate folic acid or are not able to use it very well.

The SNPs panels give information about tendencies, and they can help to determine details of treatment that might be most effective for a given person, but they alone don't determine what is actually going on. A person has the same genes before they develop ME/CFS as they have after they have become ill. The genes may give them a vulnerability, but other factors are necessary to cause the onset of this disorder.

Lately, quite a few people have gotten the 23andme.com genotype panel. It includes about 1 million SNPs, and the price is lower than the Yasko panel. It does not include all the SNPs on the Yasko panel, even though the total is a million compared to 30. It is estimated that there is a total of 10 million possible SNPs in the human genome, so even though the 23andme panel is very large, it still characterizes only about one-tenth of all the SNPs that are possible to have. But for the vast majority of these SNPs, no one yet knows what their effects are. A lot more research will need to be done to determine this. I think it will need to be focused, based on hypotheses about which parts of the metabolism are most important. There is a trend these days to do research without specific hypotheses. They call this "data mining" or "data-driven research." They are hopeful that by doing a lot of number-crunching with computers, the understanding will somehow just drop out. I personally don't believe that this is a very efficient or productive way to do science. The genome is so complicated that this approach usually doesn't lead to much in the way of understanding what is going on. I prefer what is called "hypothesis-driven" research. Developing hypotheses is more of a right-brained (combined with left-brained) activity, while the data mining is pretty much just left-brained. Computer analysis can be very helpful, but I think you have to be able to tell the computer what to look for, and that's where a hypothesis comes in. Well, so much for my philosophical rant. I hope some of this is helpful.

Best regards,

Rich

Best regards,

Rich

 

[anniekim]

Thanks very much Rich for your detailed reply, a bit clearer about it all now

 

[Freddd]

Hi, anniekim.

Quite a few people have had the methylation SNPs (sincgle nucleotide polymorphisms) panel offered by Dr. Amy Yasko (http://www.doctoramyyasko.com or more specifically,

http://www.holisticheal.com/comprehensive-methylation-panel-with-methylation-pathway-analysis.html).

It has 30 SNPs on it that she has selected. The basis for her selection is that these SNPs are associated with the methylation cycle and related pathways, and that they assist in deciding about treatment for the individual. She uses this panel primarily for treating cases of autism, but it has also been used in ME/CFS and in several of the adult neurological disorders. I initially encouraged people to try the full Yasko treatment for ME/CFS, and some people have done so. However, it is very complex and fairly expensive, so that it was not feasible for many PWMEs to use. Therefore, in early 2007, I proposed a simplified version of it. I have also encouraged people to run the Health Diagnostics and Research Institute methylation pathways panel to determine whether there is a partial methylation cycle block and glutathione depletion, and to monitor the progress of treatment. Dr. Yasko does not use this panel, but I find it to be more direct than inferring the status of these parts of the metabolism from the set of tests that she uses, including the SNPs panel. I have no objection to using the tests she recommends, and in fact, if a person has the resources to do so, they can be very helpful. But for someone who is looking for a more streamlined approach at lower cost, I favor running the methylation pathways panel, and if it shows these problems, then to try the simplified treatment approach.

In addition to the simplified methylation protocol that I have proposed, there are now several other methylation-type treatments in use by various people. Freddd, on these forums, encourages the use of a somewhat different protocol that has helped him and several others. The simplified treatment will not work for him, and apparently not for some others, either. The reasons appear to be genetic, but we have not completely nailed them down yet. I think they involve the MTHFS and the MMACHC genes. There are also other methylation-type protocols in use by various physicians. All of them have in common that they include a fairly high dose of B12, either sublingual or injected, and a more normal dosage of folate, most of them using the active forms of folate, which are 5L-methyl tetrahydrofolate and folinic acid. Some people appear not to be able to tolerate folinic acid, and some do not tolerate folic acid or are not able to use it very well.

The SNPs panels give information about tendencies, and they can help to determine details of treatment that might be most effective for a given person, but they alone don't determine what is actually going on. A person has the same genes before they develop ME/CFS as they have after they have become ill. The genes may give them a vulnerability, but other factors are necessary to cause the onset of this disorder.

Lately, quite a few people have gotten the 23andme.com genotype panel. It includes about 1 million SNPs, and the price is lower than the Yasko panel. It does not include all the SNPs on the Yasko panel, even though the total is a million compared to 30. It is estimated that there is a total of 10 million possible SNPs in the human genome, so even though the 23andme panel is very large, it still characterizes only about one-tenth of all the SNPs that are possible to have. But for the vast majority of these SNPs, no one yet knows what their effects are. A lot more research will need to be done to determine this. I think it will need to be focused, based on hypotheses about which parts of the metabolism are most important. There is a trend these days to do research without specific hypotheses. They call this "data mining" or "data-driven research." They are hopeful that by doing a lot of number-crunching with computers, the understanding will somehow just drop out. I personally don't believe that this is a very efficient or productive way to do science. The genome is so complicated that this approach usually doesn't lead to much in the way of understanding what is going on. I prefer what is called "hypothesis-driven" research. Developing hypotheses is more of a right-brained (combined with left-brained) activity, while the data mining is pretty much just left-brained. Computer analysis can be very helpful, but I think you have to be able to tell the computer what to look for, and that's where a hypothesis comes in. Well, so much for my philosophical rant. I hope some of this is helpful.

Best regards,

Rich

Best regards,

Rich

Hi Rich,

Just a comment on data-mining. It is best when there is some idea of what you are looking for. So if you go looking on the internet for everybody who says that their neuropathies have been partially or fully healed though some vitamin protocol, which is what I did in 2002, I came up with considerable numbers of people who made those claims. In reading the posts in detail, almost all included methylb12 in what they were doing, but only 5% using methylb12 were claiming any significant healing. Once I saw that 5% number, including some up from wheelchair experiences with sub acute combined degeneration, of very special interest to me and only with methylb12, I decided to chase down what made the difference. That was the 1% inspiration. The rest has been perspiration. The result was that list of things that prevents b12 therapies from being effective. So after 2 years of chasing those things down it came down to, only methylb12 consistantly produced results, only larger doses consistantly produced better results, only certain brands consistantly produced superior results. There has been a confounding factor all along which has turned out to be paradoxical folate deficiency. In those most sucessful people in addition to mb12 was typically Dibencozide, Salmon oil, (not being sold as omega3 oils yet if I remember correctly) and b-complex. What had put me onto this direction in the first place was some of the dramatic effects of the traditional Tantirc meal in a vegetarian country (I was a vegetarian remember) including beef, fish, "aphrodisiacal" whole grain dish and whatever. So in other words, adb12, mb12, omega3 fishoils, b-complex high quality protein and even some meat source folate. This is how I used data mining. Not something to randomly crunch massive data looking for shots in the dark, but very targeted searches. I started suggesting data mining in 1982 to an HMO designing their new computer system, to do active interventions, ie pull out women with a history of neonates with certain types of problems indicating vitamin deficiencies and other things doable in 1982, picking out the best outcome docs for second opinions and things like that.

After my response to glutathione, I applied the same methods looking at first for certain symptoms amd came up with "glutathione detox" reports all over the place, and "NAC detox" all over the place. It's lot's of people, not rare at all. Same with "detox" following starting folic acid containing protocols which points at paradoxical folate deficiency. It took less than 1 minute each thanks to google to find things that needed reading. And "detox" following quickly upon mb12/metafolin which adds up to low potassium. It's pretty amazing what data mining can turn up. Every thing I have added including glutathione/NAC I checked out. There was one thing lacking on the glutathione/NAC stuff. Nobody actually gets better on it. I let myself be overwhelmed by all the opinions and praise depiste the absence of the third leg of what I had applied to everything else. After all I had nailed a lot of major critical factors and I expected it to get more subtle. Also I know for sure that there was a missing factor which glutathione certainly pointed me at, induced folate deficiency. And that was a BINGO. Unfortunately it has left me with a significant amount of damage it caused. I let others' opinions sway me and I knew it as I was doing it, that I had dropped my standards. Instead of being sure it was only a probable.

Working from hypothesis is useful. Combining hypthesis with actual results is also very useful. In my consulting I was always working from indirect measures; things both there and not there. There was nothing that said "healed". But there were people who ceased meds and cut way back on doctor visits. In looking at complications rate, we had to pay attention to the complications present, but also to all those expected complications that didn't happen, all those complications, redos or revisions that were not present.

 

[snowathlete]

So this mercury detox stuff, the genes involved - can someone explain in laymans terms what i should be looking for in my 23andme dna results to see if there is a problem or not?

Now that i have my 23andme data i need to learn what to do with it. I have sent a message to PR admin asking if we can have a 'Genetics' section in the forum, as i think it would be really handy to collect information all in one place.

There probably arent m/any studies specific to ME/CFS and genes, but stuff like this is info that is available and could be really useful, even if it is preliminary data.

Is there any other known genetic data on folate, B12 and other stuff that might be related to methylation?

Which of the SNPs that are on the 23andme panal are also on the Yasko panel? and are they of any use without the others?

My guess is that 23andme will release a full genome test before too long. There is new company that is doing that now for about $1000 (600), but i dont know anything much about them. The data is only half the problem, you need to know what to look for and what it means, which is where the 23andme site is very good (but obviously only for the SNPs it tests).

Automated data mining can work, and will lead to breakthroughs, but it is dependant on good clean data, and a lot of it, and that is the difficult bit. If and when half a billion people have had their full genome done and data about which of these half billion people have which illnesses, then this method becomes very powerful, but clearly we are a long way off that!
Until there is much bigger data pools (and even when there are) driving the science with a hypothesis is a good idea, because it focuses much more the effort. However, it is only as good as the hypothesis, and so it can actually cause you to miss something. It depends on how good the hypothesis is, and that is mainly dependant on current known facts, and beliefs. Also, as Fred points out, inspiration also plays a key part, and its very difficult to teach a computer to be inspired (not as impossible, just very difficult).

And computers are just as prone to being lead by beliefs, because the people who program them are too. The good news, is that computers learn more logically than humans, so once they start finding stuff, and that stuff is confirmed, they can learn from this data and they ways they found it, and the quicker ways they might have found it, and literally start evolving its data mining itself.

People are working on this stuff now, have been for a while, but its decades away from being a practical and useful reality. I look at my daughter who is one next month, and i think, "Yeah, you will benefit from this sort of technology" and feel happy about that. I might even benefit from it in the later part of my lifetime if i am lucky.

 

[Rosebud Dairy]

I am interested in finding what SNP's I may have, as I seem to have some roadblocks working in my body, but am not sure what they are just by guesswork, of course.



@ Freddd,

SPEAKING UP HERE!

My physician is open-minded, and she and I just had an MTHFR conversation this week, in fact, in which I told her that I am going into this assuming that I am pretty much a "non-user" of folic acid. I am just letting her know that my treatment goals are to bypass that conversion altogether right now. Her clinical interest was definitely piqued. She wanted to check my blood folic acid levels (in addition to some other stuff related to chest pains) in about a month "just to see what might be going on when (I) am not strict with diet."

The fire in my feet was less this morning after I allowed myself an approximately 24 hour "washout" period for folic acid. Is this healing, low potassium, paradoxical folate deficiency, or perhaps folic acid overload? I just keep wondering what other genetics I may have going on that contribute to these problems, and those of my kids.



Happy to put this in a different thread if need be.

 

[Freddd]

I am interested in finding what SNP's I may have, as I seem to have some roadblocks working in my body, but am not sure what they are just by guesswork, of course.



@ Freddd,

SPEAKING UP HERE!

My physician is open-minded, and she and I just had an MTHFR conversation this week, in fact, in which I told her that I am going into this assuming that I am pretty much a "non-user" of folic acid. I am just letting her know that my treatment goals are to bypass that conversion altogether right now. Her clinical interest was definitely piqued. She wanted to check my blood folic acid levels (in addition to some other stuff related to chest pains) in about a month "just to see what might be going on when (I) am not strict with diet."

The fire in my feet was less this morning after I allowed myself an approximately 24 hour "washout" period for folic acid. Is this healing, low potassium, paradoxical folate deficiency, or perhaps folic acid overload? I just keep wondering what other genetics I may have going on that contribute to these problems, and those of my kids.


Happy to put this in a different thread if need be.

Hi Rosebud Dairy,

Paradoxical folate deficiency can very much increase pain, not just increase the perception of pain. The two are quite different.

Is this healing, low potassium, paradoxical folate deficiency, or perhaps folic acid overload?

That is a question that can't be answered at this point. After all the potentially confounding items are elliminated and then the changes considered in terms of adding one item at a time can an answer be arrived at.


So after removing folic acid, folinic acid, glutathione, glutathione precusros, NAC, whey and then you try various doses of Metafolin in a systematic way against a steady bacground of mb12/adb12 and vitamin and mineral basics can we judge what is going on.

Unfortunately nobody knows what these genetic things mean. When we have a few hundred people who have gone through these exacting trials and know how they all react to the various items and they all get the genetic testing that is broad enough then we might be able to correlate certain genetic characterisitics with the various responses.

Good for your doc by the way. I have always tried to educate my docs,. Some are fascinated by what is going on and some have gotten rid of me for having theories different from what they learned.

 

[richvank]

***Hi, Snow.

So this mercury detox stuff, the genes involved - can someone explain in laymans terms what i should be looking for in my 23andme dna results to see if there is a problem or not?

***I don't think anybody has this all worked out yet, but here are some comments: Normally, mercury is detoxed by being conjugated with glutathione. This is done by glutathione transferase enzymes, such as GSTM1, GSTP1, and GSTT1. There have been some papers published about studies showing that certain SNPs in them are associated with mercury detox problems, but I haven't had a chance to study them yet. You can find them on PubMed by typing mercury and GSTM1 in the search box, and then mercury and GSTP1 and so on. The problem with GSTM1 is that in a big fraction of people it is completely missing. I would think that that would show up as a blank on the GSTM1 SNPs page in the 23andme basic data, which you can access from the account box at the top of their webpage, after you sign in. Once you get to the basic data, just type GSTM1 into the SNP box and you will get that page. You can do the same for the other GST enzymes. For GSTP1, there are a couple of SNPs that are particularly suspect. They are the ones that are characterized also by the Genovations Detoxigenomic Profile. In order to check them in your 23andme data, you have to have their rs numbers, which unfortunately are often not published in the research papers, especially older ones. But I think you can find them with one of the data bases that you can access by clicking on the little box in front of "GSTP1" on each line of the data page for GSTP1. Then you have to figure out which letter corresponds to the norm, and which is the SNP. You can probably figure this out from the published papers or the referenced data bases.

***Having glutathione depleted, as is the case for most people who have ME/CFS, is going to cause problems for mercury detox, even if they don't have SNPs in the GST enzymes, but people who have such SNPs are going to have more problems with mercury detox.

Now that i have my 23andme data i need to learn what to do with it. I have sent a message to PR admin asking if we can have a 'Genetics' section in the forum, as i think it would be really handy to collect information all in one place.

***Yes, I think that would be interesting. There was actually a 23andme thread started some time ago, but it hasn't been active lately. It is here:

http://forums.phoenixrising.me/showthread.php?10973-23andme-genetic-testing&highlight=23andme

There probably arent m/any studies specific to ME/CFS and genes, but stuff like this is info that is available and could be really useful, even if it is preliminary data.

***I agree. I think there is a lot of potential in working this out.

Is there any other known genetic data on folate, B12 and other stuff that might be related to methylation?

***Yes. That's what the Yasko panel is all about.

Which of the SNPs that are on the 23andme panal are also on the Yasko panel? and are they of any use without the others?

***You can find info on that in the thread I cited above. Yes, I think they are of use, but it's important to keep in mind that they only give tendencies, and do not determine by themselves what is going to happen in the biochemistry.

**Other issues that are likely genetically determined are the intolerance of folic acid, folinic acid, glutathione, NAC, and whey protein, and inability to make use of cyano- and hydroxo-B12 that some people have, which is what Freddd and I are trying to sort out. This is on another thread that is currently active. I have posted my SNP results for the three genes that I think must be involved with these issues.

***I need to go help my wife with something now, but maybe this will give you some clues about how to approach this.

***Best regards,

***Rich