Re: SNPs in our group compared to publications

[Guest guest]

Hi Rich -

Sorry to be out of the loop, but what is an SNP?

rvankonynen wrote:

>

> Hi, all.

>

> Since quite a few people here have now gotten either the Genovations

> Detoxigenomic panel or the Yasko panel run, or both, we have some

> data for the frequency that SNPs occur in the population here that

> has gotten these tests.

>

> Just for fun, I tallied up the number of people who have the three

> SNPs on these two panels that have been found to be high in PWCs in

> published papers. These are the COMT (V158M), the ACE (Deletion

> 16), and the MAO A. The COMT SNP frequency has been found to be

> elevated in both CFS and in FM. There are two papers reporting that

> the ACE SNP is elevated in CFS. One paper reports elevation of MAO

> A SNPs in CFS.

>

> Here's what I found in our tested population:

>

> For COMT, out of sixteen PWCs for whom I have precise data, 6 are

> (+/+), 8 are (+/-), and 2 are (-/-). The percentages are thus 37.5,

> 50, and 12.5%, respectively. In the general population, I think

> these run about 16, 36 and 48%, respectively. So I think our

> population is clearly showing higher frequencies for this SNP, in

> agreement with the studies.

>

> For ACE (Deletion 16), I have data for eight PWCs, and seven out of

> the eight are (+/+) (a double deletion), none are (+/-), and one is

> (-/-), for percentages of 87.5, 0, and 12.5%, respectively. In the

> general population, I think these percentages are about 27, 46 and

> 27%, respectively. There does appear to be a higher frequency of

> this SNP in our population than in the general population, and it is

> striking that they are all double deletions, with no single

> deletions.

>

> For MAO A, I have data for six PWCs. Of these, three are (+/+) and

> three are (+/-), with no (-/-), for percentages of 50, 50, and 0%,

> respectively. I don't have a good estimate of the frequency of this

> one in the general population, but I think it is about 25% who have

> it at all. So again, it looks like a higher frequency here, as in

> the published work.

>

> Well, we don't have a really large number of people to look at, so

> the statistics aren't really great yet, but it does look as though

> the trends are there, as others have published.

>

> There are a few other SNPs that have been found to be more frequent

> in PWCs, but they aren't in these two test panels. Also, there are

> many SNPs in these panels that haven't been studied for their

> frequency in PWCs.

>

> One that really looks interesting is the CYP1B1 (V432L or N453S). I

> have data for eleven PWCs (9 women, 2 men), and EVERY ONE has this

> one! In the general population, I think it runs about half.

> Because of its role in detoxing estradiol, I suspect that this one

> will answer the old, old question of why women get CFS at rates

> about 3 to 4 times as high as men do, especially if it turns out

> that the COMT(V158M) and the GSTP1(I105V) SNPs often occur with it,

> as seems to be the case. This would set women up for an additional

> load of oxidative stress as their bodies try to process and detox

> the estradiol, and that would bias them toward greater depletion of

> glutathione, which I believe is what triggers the vicious circle

> involving the methylation cycle (for those who also have appropriate

> SNPs in enzymes there) and brings about the onset of CFS. So I'll

> be interested to see if this high incidence of the CYP1B1 SNPs holds

> up as other PWCs get the Detoxigenomic panel run. I'd be especially

> interested to hear of anyone who got this panel run and did not come

> out positive for the CYP1B1 SNP.

>

> Another thing that looks interesting in the data I currently have is

> the dreaded SNPs that upregulate the CBS enzyme, CBS(C699T) and CBS

> (A360A). Out of eight PWCs for whom I have at least partial data,

> seven have at least one copy of one of these two SNPs. I don't have

> good numbers on them for the general population, but I suspect that

> they are considerably lower.

>

> Another one that shows some indication of perhaps being higher in

> PWCs than in the general population is MTRR(A66G). Six out of eight

> have at least one copy of this one, but I think it runs fairly high

> in the general population, too (I have a figure of 47%), so it's

> hard to be sure whether it's higher in the PWC group, which such a

> small number of cases.

>

> So far I've been discussing the frequency of these SNPs

> individually, but I think the real whammy comes when several of them

> occur together in the same person, and we definitely have that

> situation. For examples, Janet and each have at least one copy

> of every SNP I've discussed here as having higher frequencies in

> PWCs, together with a few more. Probably quite a few of the others

> do, too, but I don't have both Detoxigenomic and Yasko panels for

> everyone for whom I have data.

>

> I think all of this is consistent with the proposition that genetics

> plays an important role in CFS. I think it also provides support

> for the notion that we can make a positive impact by compensating

> for the genetic variations that do occur in CFS. And it also

> provides clues about the pathogenesis of CFS.

>

> Rich

>

>

[Guest guest]

Rich,

Thank you for all the work you have been doing. I'm not sure if you

can answer this, but I'll pose the question anyway. Since the SNPs you

discuss are not specific to PWCs, what would be the reason that only

certain people get sick. I know the sample size is quite small, but if

the trend you notice continues, can you speculate if it would be a

combination of SNPs (which you mention) or possibly an exposure to a

stressor along with some combination of SNPs that result in disease?

Again, thanks for the work you're doing.

Chris

>

> Hi, all.

>

> Since quite a few people here have now gotten either the Genovations

> Detoxigenomic panel or the Yasko panel run, or both, we have some

> data for the frequency that SNPs occur in the population here that

> has gotten these tests.

>

> Just for fun, I tallied up the number of people who have the three

> SNPs on these two panels that have been found to be high in PWCs in

> published papers. These are the COMT (V158M), the ACE (Deletion

> 16), and the MAO A. The COMT SNP frequency has been found to be

> elevated in both CFS and in FM. There are two papers reporting that

> the ACE SNP is elevated in CFS. One paper reports elevation of MAO

> A SNPs in CFS.

>

> Here's what I found in our tested population:

>

> For COMT, out of sixteen PWCs for whom I have precise data, 6 are

> (+/+), 8 are (+/-), and 2 are (-/-). The percentages are thus 37.5,

> 50, and 12.5%, respectively. In the general population, I think

> these run about 16, 36 and 48%, respectively. So I think our

> population is clearly showing higher frequencies for this SNP, in

> agreement with the studies.

>

> For ACE (Deletion 16), I have data for eight PWCs, and seven out of

> the eight are (+/+) (a double deletion), none are (+/-), and one is

> (-/-), for percentages of 87.5, 0, and 12.5%, respectively. In the

> general population, I think these percentages are about 27, 46 and

> 27%, respectively. There does appear to be a higher frequency of

> this SNP in our population than in the general population, and it is

> striking that they are all double deletions, with no single

> deletions.

>

> For MAO A, I have data for six PWCs. Of these, three are (+/+) and

> three are (+/-), with no (-/-), for percentages of 50, 50, and 0%,

> respectively. I don't have a good estimate of the frequency of this

> one in the general population, but I think it is about 25% who have

> it at all. So again, it looks like a higher frequency here, as in

> the published work.

>

> Well, we don't have a really large number of people to look at, so

> the statistics aren't really great yet, but it does look as though

> the trends are there, as others have published.

>

> There are a few other SNPs that have been found to be more frequent

> in PWCs, but they aren't in these two test panels. Also, there are

> many SNPs in these panels that haven't been studied for their

> frequency in PWCs.

>

> One that really looks interesting is the CYP1B1 (V432L or N453S). I

> have data for eleven PWCs (9 women, 2 men), and EVERY ONE has this

> one! In the general population, I think it runs about half.

> Because of its role in detoxing estradiol, I suspect that this one

> will answer the old, old question of why women get CFS at rates

> about 3 to 4 times as high as men do, especially if it turns out

> that the COMT(V158M) and the GSTP1(I105V) SNPs often occur with it,

> as seems to be the case. This would set women up for an additional

> load of oxidative stress as their bodies try to process and detox

> the estradiol, and that would bias them toward greater depletion of

> glutathione, which I believe is what triggers the vicious circle

> involving the methylation cycle (for those who also have appropriate

> SNPs in enzymes there) and brings about the onset of CFS. So I'll

> be interested to see if this high incidence of the CYP1B1 SNPs holds

> up as other PWCs get the Detoxigenomic panel run. I'd be especially

> interested to hear of anyone who got this panel run and did not come

> out positive for the CYP1B1 SNP.

>

> Another thing that looks interesting in the data I currently have is

> the dreaded SNPs that upregulate the CBS enzyme, CBS(C699T) and CBS

> (A360A). Out of eight PWCs for whom I have at least partial data,

> seven have at least one copy of one of these two SNPs. I don't have

> good numbers on them for the general population, but I suspect that

> they are considerably lower.

>

> Another one that shows some indication of perhaps being higher in

> PWCs than in the general population is MTRR(A66G). Six out of eight

> have at least one copy of this one, but I think it runs fairly high

> in the general population, too (I have a figure of 47%), so it's

> hard to be sure whether it's higher in the PWC group, which such a

> small number of cases.

>

> So far I've been discussing the frequency of these SNPs

> individually, but I think the real whammy comes when several of them

> occur together in the same person, and we definitely have that

> situation. For examples, Janet and each have at least one copy

> of every SNP I've discussed here as having higher frequencies in

> PWCs, together with a few more. Probably quite a few of the others

> do, too, but I don't have both Detoxigenomic and Yasko panels for

> everyone for whom I have data.

>

> I think all of this is consistent with the proposition that genetics

> plays an important role in CFS. I think it also provides support

> for the notion that we can make a positive impact by compensating

> for the genetic variations that do occur in CFS. And it also

> provides clues about the pathogenesis of CFS.

>

> Rich

>

[Guest guest]

Hi, Colin.

SNP stands for single nucleotide polymorphism. It is a mutation in

a gene that involves a change in one nucleotide in the DNA

molecule. In the entire human genome of about 35,000 genes, there

are estimated to be over 10 million different SNPs in the entire

human population. We all inherit SNPs from our parents. Different

people have different SNPs. Certain SNPs have been found to be

associated with greater likelihood of having certain diseases. This

is true in autism, and it appears that the same SNPs that are

important in autism are important in CFS. The Yasko panel has been

developed particularly for autism, but quite a few people with CFS

(PWCs) have been ordering it lately. The Detoxigenomic panel looks

for SNPS in enzymes involved with the detoxication system in the

body. This system appears to be very relevant in many cases of CFS

as well, so quite a few people here have also gotten that panel. I

hope this clarifies things.

Rich

> >

> > Hi, all.

> >

> > Since quite a few people here have now gotten either the

Genovations

> > Detoxigenomic panel or the Yasko panel run, or both, we have some

> > data for the frequency that SNPs occur in the population here

that

> > has gotten these tests.

> >

> > Just for fun, I tallied up the number of people who have the

three

> > SNPs on these two panels that have been found to be high in PWCs

in

> > published papers. These are the COMT (V158M), the ACE (Deletion

> > 16), and the MAO A. The COMT SNP frequency has been found to be

> > elevated in both CFS and in FM. There are two papers reporting

that

> > the ACE SNP is elevated in CFS. One paper reports elevation of

MAO

> > A SNPs in CFS.

> >

> > Here's what I found in our tested population:

> >

> > For COMT, out of sixteen PWCs for whom I have precise data, 6 are

> > (+/+), 8 are (+/-), and 2 are (-/-). The percentages are thus

37.5,

> > 50, and 12.5%, respectively. In the general population, I think

> > these run about 16, 36 and 48%, respectively. So I think our

> > population is clearly showing higher frequencies for this SNP, in

> > agreement with the studies.

> >

> > For ACE (Deletion 16), I have data for eight PWCs, and seven out

of

> > the eight are (+/+) (a double deletion), none are (+/-), and one

is

> > (-/-), for percentages of 87.5, 0, and 12.5%, respectively. In

the

> > general population, I think these percentages are about 27, 46

and

> > 27%, respectively. There does appear to be a higher frequency of

> > this SNP in our population than in the general population, and

it is

> > striking that they are all double deletions, with no single

> > deletions.

> >

> > For MAO A, I have data for six PWCs. Of these, three are (+/+)

and

> > three are (+/-), with no (-/-), for percentages of 50, 50, and

0%,

> > respectively. I don't have a good estimate of the frequency of

this

> > one in the general population, but I think it is about 25% who

have

> > it at all. So again, it looks like a higher frequency here, as in

> > the published work.

> >

> > Well, we don't have a really large number of people to look at,

so

> > the statistics aren't really great yet, but it does look as

though

> > the trends are there, as others have published.

> >

> > There are a few other SNPs that have been found to be more

frequent

> > in PWCs, but they aren't in these two test panels. Also, there

are

> > many SNPs in these panels that haven't been studied for their

> > frequency in PWCs.

> >

> > One that really looks interesting is the CYP1B1 (V432L or

N453S). I

> > have data for eleven PWCs (9 women, 2 men), and EVERY ONE has

this

> > one! In the general population, I think it runs about half.

> > Because of its role in detoxing estradiol, I suspect that this

one

> > will answer the old, old question of why women get CFS at rates

> > about 3 to 4 times as high as men do, especially if it turns out

> > that the COMT(V158M) and the GSTP1(I105V) SNPs often occur with

it,

> > as seems to be the case. This would set women up for an

additional

> > load of oxidative stress as their bodies try to process and detox

> > the estradiol, and that would bias them toward greater depletion

of

> > glutathione, which I believe is what triggers the vicious circle

> > involving the methylation cycle (for those who also have

appropriate

> > SNPs in enzymes there) and brings about the onset of CFS. So I'll

> > be interested to see if this high incidence of the CYP1B1 SNPs

holds

> > up as other PWCs get the Detoxigenomic panel run. I'd be

especially

> > interested to hear of anyone who got this panel run and did not

come

> > out positive for the CYP1B1 SNP.

> >

> > Another thing that looks interesting in the data I currently

have is

> > the dreaded SNPs that upregulate the CBS enzyme, CBS(C699T) and

CBS

> > (A360A). Out of eight PWCs for whom I have at least partial data,

> > seven have at least one copy of one of these two SNPs. I don't

have

> > good numbers on them for the general population, but I suspect

that

> > they are considerably lower.

> >

> > Another one that shows some indication of perhaps being higher in

> > PWCs than in the general population is MTRR(A66G). Six out of

eight

> > have at least one copy of this one, but I think it runs fairly

high

> > in the general population, too (I have a figure of 47%), so it's

> > hard to be sure whether it's higher in the PWC group, which such

a

> > small number of cases.

> >

> > So far I've been discussing the frequency of these SNPs

> > individually, but I think the real whammy comes when several of

them

> > occur together in the same person, and we definitely have that

> > situation. For examples, Janet and each have at least one

copy

> > of every SNP I've discussed here as having higher frequencies in

> > PWCs, together with a few more. Probably quite a few of the

others

> > do, too, but I don't have both Detoxigenomic and Yasko panels for

> > everyone for whom I have data.

> >

> > I think all of this is consistent with the proposition that

genetics

> > plays an important role in CFS. I think it also provides support

> > for the notion that we can make a positive impact by compensating

> > for the genetic variations that do occur in CFS. And it also

> > provides clues about the pathogenesis of CFS.

> >

> > Rich

> >

> >

>

>

>

>

[Guest guest]

Hi Rich-when you say " we can make a positive impact by compensating

for the genetic variations " , does that mean a potential experimental

treatment? If so, are we talking stem cells, herbs, minerals

vitamins, etc. Your research is excellent, but I think there are

a few simple minded list members like myself who need

non-technical info. if you are amenable to doing that. Thanks,

Mike C

> I think all of this is consistent with the proposition that genetics

> plays an important role in CFS. I think it also provides support

> for the notion that we can make a positive impact by compensating

> for the genetic variations that do occur in CFS. And it also

> provides clues about the pathogenesis of CFS.

>

> Rich

>

[Guest guest]

Hi, Mike.

I'm referring to the same treatments that are used in autism by the

DAN! project and by Dr. Amy Yasko. They include various

specifically targeted supplements, herbs, and occasionally some

pharmaceuticals. But the main approaches involve nonprescription

items.

I prefer Dr. Yasko's approach, because she characterizes the

particular SNPs each person has, and then designs the treatment

program to match them.

If you read the message I just posted to Joyce Kaye, you can get an

idea of what the treatment is like. Of course, what I wrote to her

is meant for a person who has the CBS upregulation. If you don't

have that, then you would start out differently, because you

wouldn't have to worry about the ammonia and sulfite. It's kind of

involved, and it takes some study on the part of the person who

wants to do it. But I think the potential of getting at the root

causes and realizing some fundamental improvement is very high with

this approach.

Rich

> > I think all of this is consistent with the proposition that

genetics

> > plays an important role in CFS. I think it also provides

support

> > for the notion that we can make a positive impact by

compensating

> > for the genetic variations that do occur in CFS. And it also

> > provides clues about the pathogenesis of CFS.

> >

> > Rich

> >

>

[Guest guest]

Hi, Chris.

You are very welcome!

Yes, it looks as though the onset of CFS, at least in the

nonepidemic (aka sporadic) cases, requires two things: first, one of

a set of combinations of SNPs that predispose the person (make them

vulnerable), and second, factors or circumstances in their life

(stressors is another word for them, but it's kind of unpopular to

some people here!) that raise their cortisol for an extended time,

and also lower their glutathione sufficiently to trigger a vicious

circle mechanism that is made possible by their combination of

SNPs.

There are several different combinations of SNPs that will

predispose a person, and they account for some of the different

subsets that have been observed within CFS.

>

> Rich,

>

> Thank you for all the work you have been doing. I'm not sure if you

> can answer this, but I'll pose the question anyway. Since the SNPs

you

> discuss are not specific to PWCs, what would be the reason that

only

> certain people get sick. I know the sample size is quite small,

but if

> the trend you notice continues, can you speculate if it would be a

> combination of SNPs (which you mention) or possibly an exposure to

a

> stressor along with some combination of SNPs that result in

disease?

>

> Again, thanks for the work you're doing.

>

> Chris

[Guest guest]

Hi, Louella.

>

> Rich

>

> I take it that there's no point in taking either of these snp

panels unless one is willing to follow through with the Yasko DVDs

and protocol. Is that correct?

***Well, I guess it would depend on what your goal was. If you have

CFS, I'm assuming that your goal would be to get better. If so,

then I think that Dr. Yasko's approach offers hope to do that, and

if you know what your SNPs are specifically, you can target them

with particular supplements. That's the reason to characterize the

SNPs. On the other hand, if you just wanted to know what your SNPs

are, you could do the panels and not do the treatment. I can't

imagine why someone would do that if they had CFS, since it isn't

cheap and it doesn't make you better, but it's certainly an option.

There's no obligation to do the treatment.

>

> also, presumably one could figure out if there was a problem

building glutathione simply by supplementing with it for a while and

then testing intracellular levels of it and comparing that against a

baseline test?

***Well, yes. I advocated that approach for several years, and it

actually did work for a small number of people on this list.

However, for most PWCs, while it helps some with the quality of

life, it doesn't break the vicious circle and it provides job

security for those who supply the glutathione. The subset who has a

CBS upregulation usually can't tolerate much glutathione or whey

protein, or NAC, so this approach really doesn't even help their QOL

very much.

>

> Louella

***Rich

[Guest guest]

Hi, Louella.

>

> Rich

>

> I take it that there's no point in taking either of these snp

panels unless one is willing to follow through with the Yasko DVDs

and protocol. Is that correct?

***Well, I guess it would depend on what your goal was. If you have

CFS, I'm assuming that your goal would be to get better. If so,

then I think that Dr. Yasko's approach offers hope to do that, and

if you know what your SNPs are specifically, you can target them

with particular supplements. That's the reason to characterize the

SNPs. On the other hand, if you just wanted to know what your SNPs

are, you could do the panels and not do the treatment. I can't

imagine why someone would do that if they had CFS, since it isn't

cheap and it doesn't make you better, but it's certainly an option.

There's no obligation to do the treatment.

>

> also, presumably one could figure out if there was a problem

building glutathione simply by supplementing with it for a while and

then testing intracellular levels of it and comparing that against a

baseline test?

***Well, yes. I advocated that approach for several years, and it

actually did work for a small number of people on this list.

However, for most PWCs, while it helps some with the quality of

life, it doesn't break the vicious circle and it provides job

security for those who supply the glutathione. The subset who has a

CBS upregulation usually can't tolerate much glutathione or whey

protein, or NAC, so this approach really doesn't even help their QOL

very much.

>

> Louella

***Rich

[Guest guest]

" rvankonynen " <richvank@...> wrote:

> Yes, it looks as though the onset of CFS, at least in the

nonepidemic (aka sporadic) cases, requires two things: first, one

of a set of combinations of SNPs that predispose the person (make

them vulnerable), and second, factors or circumstances in their life

(stressors is another word for them, but it's kind of unpopular to

some people here!) that raise their cortisol for an extended time,

and also lower their glutathione sufficiently to trigger a vicious

circle mechanism that is made possible by their combination of

SNPs.

>

Rich,

No bad job, marriage, burnout, Auschwitz, or any " stress " known to

mankind has ever consistently or even sporadically caused " CFS " .

If someone is shot, stabbed, overwhelmed by infection or toxic

exposure, these things are not called " stressors " .

They are called trauma or infections.

If someone gets West Nile virus, no one says the real cause of their

illness and death is from the " stress " of having West Nile virus.

This " Damned Disease " or " Living Hell " that came to be called CFS is

no different.

If anyone expresses it otherwise, and insists upon concepts that

this is some kind of normal illness that can result from an overload

of " anything and everything " , the only logical conclusion is that

they cannot be referring to an illness that stomps the living crap

out of peoples lives in a way that nobody seems to recognize, no

matter what their burden of stress or stressors.

If someone is absolutely insistent that stressors can cause CFS, I

have no other choice but to conclude that they must be thinking about

a type of illness that stress can cause - and that isn't CFS.

At least, not " original CFS " .

-

[Guest guest]

Hi, Rich.

Very interesting to see SNP trends begin to emerge specifically for PWCs. I

also happen to have the CYP1B1 SNP as found by Genovations testing, which I

don't recall mentioning before to you or anyone on this list.

I had previously reported my having SNPs for GSTM1(null), a COMT(V158M) +-,

MTHFR +- and a IL1B1 ++ which seem could contribute to CFS pathogenesis along

with the notorious CYP2C9 SNP also thrown into the mix. The IL1B1 is connected

to low stomach acid, inflammation there as well as h. pylori infection(which

I've had) and gastric cancer.

I've also tested extremely low in ferritin, which seems consistent with low

glutathione leading to malabsorbtion of iron in the gut that you've posited on

this list could occur from this. Anyway, I now count five SNPs(six if CYP2C9 is

included as extra trouble when these others are present) for my case of CFS that

seem to fit your hypothesis for CFS pathogenesis and I haven't even done Dr

Yasko testing4health.com basic SNPs panel for all that might discovered with it.

Also interesting to note I think with this data and the " debatelogue " on this

list regarding this " SNPs for CFS " topic is Dr Cheney emphasized to me in my

visit with him in 2002 that SNPs for MTHFR ARE the cause of cervical cancer, not

the human herpes papilloma virus(HHPV) popularly attributed as cause. He had

just attended a researcher's seminar that covered this the week or two before my

appointment with him that convinced him conclusively that this was the case.

Of course HHPV must be a factor, but I think his point, along side wanting to

emphasize SNPs as quite worthy suspects contributing to CFS, was that with the

good methylation that comes with good MTHFR genes HHPV simply can't take

advantage and create cervical cancer, plain and simple. I don't know how often

a single SNP will be linked as causal to a single serious disease like this, but

it is suggestive of how important SNPs are to health or lack of it as one

encounters all that one might encounter in a lifetime.

[Guest guest]

, one valid question for me is this:

Let's say what pushed one over the line was an infection. In my case,

the first blow was mercury poisoning from lots of amalgams as a teen

after braces were removed--since I distinctly recall a change in my

health and well being at that point, and so I figure I have poor detox

for mercury, genetically.

Then I'm carrying that vulnerability around and get a tickbite.

And then I get a second tickbite with babesia added in.

Okay, successive blows. The question is, had my

methylation/glutathione pathways been fully working would I have

detoxed that mercury as a teen and sallied forth with a very

functional immune system, and would the first tickbite not have caused

problems (which it did but nobody diagnosed as lyme, but as various

episodic health issues,a bit mysterious and sometimes very

frustrating but not disabling). And if not for both of those problems,

would the second tickbite have been so devastating, or could I have

taken enough drugs for a few months and gone on with my life as many do?

And now , six years later, would restoring my pathways, dumping my

mercury, return my immune system to a piont where it would

self-correct back to health, or if not, where I would be able to add

in say, herbs from Buhner's protocols to good effect, or if

necessary, some drugs?

Whereas now I cannot do that. Let's say the mercury has impaired my

porphyrin synthesis--thus my heme and my p450 detox, and that I also

may have some genetic p450 problems.

Finding out about these genetic vulnerabilities could be very

valuable, and repairing the pathways.

>

> > Yes, it looks as though the onset of CFS, at least in the

> nonepidemic (aka sporadic) cases, requires two things: first, one

> of a set of combinations of SNPs that predispose the person (make

> them vulnerable), and second, factors or circumstances in their life

> (stressors is another word for them, but it's kind of unpopular to

> some people here!) that raise their cortisol for an extended time,

> and also lower their glutathione sufficiently to trigger a vicious

> circle mechanism that is made possible by their combination of

> SNPs.

> >

>

> Rich,

> No bad job, marriage, burnout, Auschwitz, or any " stress " known to

> mankind has ever consistently or even sporadically caused " CFS " .

> If someone is shot, stabbed, overwhelmed by infection or toxic

> exposure, these things are not called " stressors " .

> They are called trauma or infections.

> If someone gets West Nile virus, no one says the real cause of their

> illness and death is from the " stress " of having West Nile virus.

> This " Damned Disease " or " Living Hell " that came to be called CFS is

> no different.

> If anyone expresses it otherwise, and insists upon concepts that

> this is some kind of normal illness that can result from an overload

> of " anything and everything " , the only logical conclusion is that

> they cannot be referring to an illness that stomps the living crap

> out of peoples lives in a way that nobody seems to recognize, no

> matter what their burden of stress or stressors.

> If someone is absolutely insistent that stressors can cause CFS, I

> have no other choice but to conclude that they must be thinking about

> a type of illness that stress can cause - and that isn't CFS.

> At least, not " original CFS " .

> -

>

[Guest guest]

Rich,

So if someone doesn't want to do the testing, for whatever reason, can

people assume they have the most common SNPs and supplement

accordingly, or are the tests absolutely necessary?

Thanks,

Chris

> >

> > Rich,

> >

> > Thank you for all the work you have been doing. I'm not sure if you

> > can answer this, but I'll pose the question anyway. Since the SNPs

> you

> > discuss are not specific to PWCs, what would be the reason that

> only

> > certain people get sick. I know the sample size is quite small,

> but if

> > the trend you notice continues, can you speculate if it would be a

> > combination of SNPs (which you mention) or possibly an exposure to

> a

> > stressor along with some combination of SNPs that result in

> disease?

> >

> > Again, thanks for the work you're doing.

> >

> > Chris

>

[Guest guest]

Hi Rich,

These are very interesting observations.

I was wondering what you mean when you say:

" One that really looks interesting is the CYP1B1 (V432L or N453S). I

have data for eleven PWCs (9 women, 2 men), and EVERY ONE has this

one! In the general population, I think it runs about half.

Because of its role in detoxing estradiol, I suspect that this one

will answer the old, old question of why women get CFS at rates

about 3 to 4 times as high as men do, especially if it turns out

that the COMT(V158M) and the GSTP1(I105V) SNPs often occur with it,

as seems to be the case. This would set women up for an additional

load of oxidative stress as their bodies try to process and detox

the estradiol, and that would bias them toward greater depletion of

glutathione, which I believe is what triggers the vicious circle

involving the methylation cycle (for those who also have appropriate

SNPs in enzymes there) and brings about the onset of CFS "

Do you mean the low glutathione hinders the recycling of B12 to

methylB12 causing a block at the methionine synthesase enzyme ?

[Guest guest]

Jill-Not putting words in Rich's or anyone else's mouth, but

according to Rich's recent theory, you could say that in addition

to the faulty genetics, the tickbites were the additional

'stressors' that more or less pushed you over the edge into what

is called 'CFS'. For some, faulty genetics and prolonged

adrenal stress could be enough.

What I am having a problem with is that if SNPs are irregular and

therefore a genetic componet is probable as a cause of CFS, are

herbs and vitamins per the Yasko protocol going to be enough to

restore us to good health? Seems like it will take a bit more than

that. However, I haven't followed the Yasko treatment protocol

closely, and will give it more study per Rich's recent response to

my related question which I greatly appreciate.

Mike C

>

> , one valid question for me is this:

>

> Let's say what pushed one over the line was an infection. In my

case,

> the first blow was mercury poisoning from lots of amalgams as a

teen

> after braces were removed--since I distinctly recall a change in my

> health and well being at that point, and so I figure I have poor

detox

> for mercury, genetically.

>

> Then I'm carrying that vulnerability around and get a tickbite.

>

> And then I get a second tickbite with babesia added in.

>

> Okay, successive blows. The question is, had my

> methylation/glutathione pathways been fully working would I have

> detoxed that mercury as a teen and sallied forth with a very

> functional immune system, and would the first tickbite not have

caused

> problems (which it did but nobody diagnosed as lyme, but as

various

> episodic health issues,a bit mysterious and sometimes very

> frustrating but not disabling). And if not for both of those

problems,

> would the second tickbite have been so devastating, or could I have

> taken enough drugs for a few months and gone on with my life as

many do?

<<snip<<<

[Guest guest]

I think you're right. If you restore your pathways, some of the

symptoms of the infection may improve and you also may be better able

to handle interventions like strong herbs or antibiotics.

> >

> > , one valid question for me is this:

> >

> > Let's say what pushed one over the line was an infection. In my

> case,

> > the first blow was mercury poisoning from lots of amalgams as a

> teen

> > after braces were removed--since I distinctly recall a change in my

> > health and well being at that point, and so I figure I have poor

> detox

> > for mercury, genetically.

> >

> > Then I'm carrying that vulnerability around and get a tickbite.

> >

> > And then I get a second tickbite with babesia added in.

> >

> > Okay, successive blows. The question is, had my

> > methylation/glutathione pathways been fully working would I have

> > detoxed that mercury as a teen and sallied forth with a very

> > functional immune system, and would the first tickbite not have

> caused

> > problems (which it did but nobody diagnosed as lyme, but as

> various

> > episodic health issues,a bit mysterious and sometimes very

> > frustrating but not disabling). And if not for both of those

> problems,

> > would the second tickbite have been so devastating, or could I have

> > taken enough drugs for a few months and gone on with my life as

> many do?

> <<snip<<<

>

[Guest guest]

" jill1313 " <jenbooks13@...> wrote:

> Finding out about these genetic vulnerabilities could be very

> valuable, and repairing the pathways.

Of course, just as the pharmaceutical companies wish to create genetic

profiles to determine who will have a positive response to chemotherapy.

And I surely want all the help I can get, countoured to my own genetic

makeup.

But...

Calling CFS " genetic " is like leaving the flood out of the equation and

saying that drowning is genetic, since some people are " born swimmers "

and would survive while the " drowners " are not.

If there was not flood, a genetic superiority or weakness doesn't

mattter.

Relying on inherited prowess to swim better is scant comfort and a

rather bizarre way of responding to a rising tide.

Individual susceptibilities aside, this illness raged through and

struck down people like an epidemic rather than an " inherited illness " .

Why would it occur to anyone to " de-emphasize " the manner in which

this illness spreads and utterly fails to respect the limitations of

genetic illnesses.

This is how Polly Murray must have felt when she went to doctors

repeatedly asking how a " genetic illness " of " JRA " could possibly be

acting like an epidemic and defying statistical probability so

dramatically, and having these doctors refuse to recognize that genetic

illnesses have to act like genetic illnesses.

Why isn't everyone here saying this?

Didn't we all see this epidemic blaze to life and spread like wildfire?

-

[Guest guest]

, I've thought a lot about this and I have no answer. I know a

family where all 4 got lyme and friends (coinfections) tho the younger

son had the mildest case, the older son almost died (misdiagnosed for

9 years), both parents got it, one parent is now basically well after

four years of high dose orals....BUT the family next door never had

it. So what is that about? The ticks observed suburban boundaries???

I don't know what to say. There is a mix of genetics and bugs that is

a mystery. I think if you can take antibiotics, or antimalarials, or

antivirals, or whatever is necessary, and get well, that's great. If

you can avoid molds and that works,well, at least it works. But for

now I'm going to focus on the genetics and see what happens when I

correct for them. At the very least I should be able to handle the

drugs better at that point. For instance, if mercury poisoning has

screwed up my porphyrin cycle, it also has screwed up my p450 detox

system. Get that back in sync and maybe I can take more drugs. Etc.

>

> > Finding out about these genetic vulnerabilities could be very

> > valuable, and repairing the pathways.

>

>

> Of course, just as the pharmaceutical companies wish to create genetic

> profiles to determine who will have a positive response to chemotherapy.

> And I surely want all the help I can get, countoured to my own genetic

> makeup.

>

> But...

>

> Calling CFS " genetic " is like leaving the flood out of the equation and

> saying that drowning is genetic, since some people are " born swimmers "

> and would survive while the " drowners " are not.

>

> If there was not flood, a genetic superiority or weakness doesn't

> mattter.

> Relying on inherited prowess to swim better is scant comfort and a

> rather bizarre way of responding to a rising tide.

>

> Individual susceptibilities aside, this illness raged through and

> struck down people like an epidemic rather than an " inherited illness " .

> Why would it occur to anyone to " de-emphasize " the manner in which

> this illness spreads and utterly fails to respect the limitations of

> genetic illnesses.

>

> This is how Polly Murray must have felt when she went to doctors

> repeatedly asking how a " genetic illness " of " JRA " could possibly be

> acting like an epidemic and defying statistical probability so

> dramatically, and having these doctors refuse to recognize that genetic

> illnesses have to act like genetic illnesses.

>

> Why isn't everyone here saying this?

> Didn't we all see this epidemic blaze to life and spread like wildfire?

> -

>

[Guest guest]

> This is how Polly Murray must have felt when she went to doctors

> repeatedly asking how a " genetic illness " of " JRA " could possibly be

> acting like an epidemic and defying statistical probability so

> dramatically, and having these doctors refuse to recognize that

genetic

> illnesses have to act like genetic illnesses.

>

> Why isn't everyone here saying this?

> Didn't we all see this epidemic blaze to life and spread like

wildfire?

> -

,

I think I have been saying this. I am not sure it is what folks want

to hear. I will be glad to see results based on using various

treatments to match various genetics. However, when I see the

treatments they look a lot like treatments many have been trying for

over a decade. Results remain to be seen. I am watching but not

jumping in - hey, I may not be genetically a good swimmer.

a

[Guest guest]

Hi, .

I think you may be right about at least a lot of the cases

of " original CFS, " as you put it, i.e. the epidemic cases. But there

are many sporadic cases within the fold, also.

Rich

> If someone is absolutely insistent that stressors can cause CFS, I

> have no other choice but to conclude that they must be thinking

about

> a type of illness that stress can cause - and that isn't CFS.

> At least, not " original CFS " .

> -

>

[Guest guest]

Hi, .

Thanks for the information. We do seem to be getting quite a

pattern of SNPs. You're right, I didn't realize that you had a

CYP1B1 SNP also. I'll add you to the list!

Rich

>

> Hi, Rich.

>

>

>

> Very interesting to see SNP trends begin to emerge specifically

for PWCs. I also happen to have the CYP1B1 SNP as found by

Genovations testing, which I don't recall mentioning before to you

or anyone on this list.

>

>

>

> I had previously reported my having SNPs for GSTM1(null), a COMT

(V158M) +-, MTHFR +- and a IL1B1 ++ which seem could contribute to

CFS pathogenesis along with the notorious CYP2C9 SNP also thrown

into the mix. The IL1B1 is connected to low stomach acid,

inflammation there as well as h. pylori infection(which I've had)

and gastric cancer.

>

>

>

> I've also tested extremely low in ferritin, which seems consistent

with low glutathione leading to malabsorbtion of iron in the gut

that you've posited on this list could occur from this. Anyway, I

now count five SNPs(six if CYP2C9 is included as extra trouble when

these others are present) for my case of CFS that seem to fit your

hypothesis for CFS pathogenesis and I haven't even done Dr Yasko

testing4health.com basic SNPs panel for all that might discovered

with it.

>

>

>

> Also interesting to note I think with this data and

the " debatelogue " on this list regarding this " SNPs for CFS " topic

is Dr Cheney emphasized to me in my visit with him in 2002 that SNPs

for MTHFR ARE the cause of cervical cancer, not the human herpes

papilloma virus(HHPV) popularly attributed as cause. He had just

attended a researcher's seminar that covered this the week or two

before my appointment with him that convinced him conclusively that

this was the case.

>

>

>

> Of course HHPV must be a factor, but I think his point, along side

wanting to emphasize SNPs as quite worthy suspects contributing to

CFS, was that with the good methylation that comes with good MTHFR

genes HHPV simply can't take advantage and create cervical cancer,

plain and simple. I don't know how often a single SNP will be

linked as causal to a single serious disease like this, but it is

suggestive of how important SNPs are to health or lack of it as one

encounters all that one might encounter in a lifetime.

>

>

>

>

>

[Guest guest]

Hi, Chris.

Yes, a person can try to " wing it " without characterizing the SNPs in

their genes. In fact, this has been the approach used in autism by

the DAN! project. If you can get some testing done, such as the urine

organic acids test or an amino acids test, it will at least give you

clues about which subset you might be in, and that's helpful.

If you don't do any testing at all, then you can try to rely on your

symptoms and responses to foods. I posted some things you can look a

couple of times a while back, and here's an updated list.

1. Are you sensitive to sulfur-containing foods in general, such as

the broccoli family, onions, garlic and eggs? (If " yes, " it would

suggest overloading of your sulfoxidation pathway, which could be

caused by a CBS upregulation SNP, and which might be

helped to some degree by taking molybdenum.)

2. How do you respond to eating a lot of protein? (If it gives you

neurological problems, or wipes you out, or puts you into a trance or

a state of torpor, you may have a CBS upregulation SNP. Cutting back

on protein and sulfur sources and taking measures to clear ammonia

from your body, such as activated charcoal and yucca, may help.)

3. Do you have sleep problems? (If " yes, " it could be caused by

problems in making serotonin and/or melatonin, and that could be a

result of a methylation block and/or a shortage of

tetrahydrobiopterin, which in turn could result from a reverse MTHFR

SNP.

4. Do you experience a lot of pain? (If " yes, " it could also be due to

low serotonin. See 3 above.)

5. Do you experience mood problems? (If " yes, " it could also be due to

low serotonin. See 3 above.)

6. Do you experience constipation? (If " yes, " it could be due to low

serotonin in the gut. See 3 above.)

7. How do you respond to supplements containing cysteine or

methionine, such as whey protein or NAC? (If these cause you problems,

you may have a CBS upregulation SNP.)

8. How do you respond to taking SAMe? (If you don't respond well to

it, you could have a CBS upregulation SNP.)

9. How do you respond to taking 5-HTP or tryptophan? (If these cause

you problems, it may suggest that your methylation cycle is blocked,

so that you are not able to use them to make serotonin very well.)

10. Do you receive any benefit from taking supplements that support

the sulfur metabolism, such as B12, B6, folic acid,(or active forms

of these, i.e. methyl B12, pyridoxal-5-phosphate, and folinic

acid or FolaPro) trimethylglycine, dimethylglycine, or magnesium?

(If " yes, " this would suggest that you have a methylation cycle or

transsulfuration pathway block. This is of course begging the

question, but some people have already tried these things and do know

if it helped them or not.)

11. Is your homocysteine level high, low, or normal? This can be

measured by conventional medical laboratories. (If it's high or

low, you may have a block. High would suggest a block in

transsulfuration, which may be helped by trying B6, or better yet, P-

5-P (the active form of B6) together with magnesium. Low would

suggest a block at methionine synthase, and might be helped by

methyl B12, folinic acid, and/or trimethylglycine. A normal

homocysteine level doesn't necessarily mean that you are in the

clear.)

12. If you've measured it, what is your plasma sulfate concentration?

This can be measured by conventional medical laboratories. (If it is

below normal, this suggests problems in your sulfur metabolism. It

could be a problem in your methylation cycle, or in your

transsulfuration pathway, or in your sulfoxidation pathway, or your

kidneys could be wasting sulfate into your urine, which can be caused

by mercury blocking the enzyme that's supposed to reabsorb sulfate.)

13. What is your 24-hour urinary creatinine excretion? This can be

measured by conventional laboratories. If it's low, it suggests

either a low methylation capacity or an overload of your urea cycle

because of a CBS upregulation.

14. Are you low in glutathione? This can be measured in red blood

cells by http://www.immuno-sci-lab.com for less than $100. (A " yes "

answer would suggest that there is a block in methylation, because

these tend to be tied together.)

15. Are you high in mercury or other heavy metals? This can be

measured by a urinary porphryins test or a DMSA-provoked urine

collection test, as offered by http://www.doctorsdata.com. I wouldn't

suggest running the latter unless your glutathione level is in the

normal range. (If " yes, " this probably means that at least you were

low in glutathione in the past, and that could infer that you have or

had a methylation cycle block. Also, mercury can directly block

enzymes. So detoxing the mercury from your body may be part of the

solution to the block, but the other supplements might help as well.)

16. Have you had a urinary organic acids test (such as from

http://www.greatplainslaboratory.com or http://www.metametrix.com) or

a metabolic analysis panel (from http://www.gsdl.com) that measured 5-

hydroxyindoleacetic acid, homovanillic acid and vanilmandelic acid,

and if so, how did it come out? (These are the metabolic breakdown

products of serotonin, dopamine and and epinephrine/norepinephrine,

respectively.) (If they are low, that would suggest that your body is

not making enough of these neurotransmitters. That could be caused by

a block in methylation.)

17. Also in the urinary organic acids test, did you have elevated

methylmalonic acid or formiminoglutamic acid (FIGLU)? (If so, you

may have a methylation cycle block, which might be helped by methyl

B12 or folinic acid, or both.)

18. What is your plasma cysteine concentration? This can be measured

in a comprehensive detox panel by http://www.gsdl.com. (If it is

high, there could be a problem in sulfoxidation or in synthesis of

glutathione. If it is low, there could be a methylation cycle

block. A high ratio of cysteine to sulfate in the plasma

would suggest a sulfoxidation problem. If so, you might try

molybdenum.)

19. What is your plasma taurine concentration? This can be measured

in a plasma amino acids test, such as offered by

http://www.doctorsdata.com. (If low or high, it would suggest

problems higher up in your sulfur metabolism. It could be

in the methylation cycle, or in the transsulfuration pathway.)

20. Also from a plasma amino acids test, what is your plasma

methionine concentration? (If it's high or low, it

suggests a methylation cycle block.)

21. What is your urinary sarcosine level? If it's high, it suggests a

shortage of tetrahydrofolate, which may mean a methylation

cycle/folate metabolism block.

22. What is your urinary serine to glycine ratio? If it is high, that

suggests that there is a bottleneck in the folate metabolism.

23. What is your ratio of urinary phenylalanine to tyrosine? If it is

high, that suggests a shortage of tetrahydrobiopterin.

24. What is your urinary ammonia level? If it is high, it suggests a

CBS upregulation SNP.

I hope this helps.

Rich

>

> Rich,

>

> So if someone doesn't want to do the testing, for whatever reason,

can

> people assume they have the most common SNPs and supplement

> accordingly, or are the tests absolutely necessary?

>

> Thanks,

> Chris

[Guest guest]

Hi, .

I think that there's more than one way that low glutathione can hook

into a methylation cycle that is weakened by having certain SNPs.

One way would be that if there is a shortage of methyl B12, such as

because of an upregulation SNP in methionine synthase or a

downregulation SNP in methionine synthase reductase, then lowering

glutathione would make this worse, since glutathione is needed to

make methyl B12 from other forms of B12. Also, methionine synthase

is a redox-sensitive enzyme. So lowering glutathione would make

conditions more oxizing, and that would inhibit the enzyme. There

are other enzymes in the methylation cycle that are also redox-

sensitive, such as the one that converts methionine to SAMe. I

don't think I understand all the ways this feedback can occur yet,

but it seems to be very real.

Rich

>

> Hi Rich,

>

> These are very interesting observations.

>

> I was wondering what you mean when you say:

>

> " One that really looks interesting is the CYP1B1 (V432L or N453S).

I

> have data for eleven PWCs (9 women, 2 men), and EVERY ONE has this

> one! In the general population, I think it runs about half.

> Because of its role in detoxing estradiol, I suspect that this one

> will answer the old, old question of why women get CFS at rates

> about 3 to 4 times as high as men do, especially if it turns out

> that the COMT(V158M) and the GSTP1(I105V) SNPs often occur with

it,

> as seems to be the case. This would set women up for an additional

> load of oxidative stress as their bodies try to process and detox

> the estradiol, and that would bias them toward greater depletion

of

> glutathione, which I believe is what triggers the vicious circle

> involving the methylation cycle (for those who also have

appropriate

> SNPs in enzymes there) and brings about the onset of CFS "

>

>

>

> Do you mean the low glutathione hinders the recycling of B12 to

> methylB12 causing a block at the methionine synthesase enzyme ?

>

>

>

>

>

>

>

>

>

>

>

>

[Guest guest]

Hi, Mike.

I think the key point here is that some of these SNPs are in enzymes

that convert one form of a nutrient, such as folic acid or B12 or B6,

from its inactive form to one of its active forms. In that case, it's

possible to give your body the active form, and just " leapfrog " over

the enzyme that isn't working well.

In other cases, if an enzyme is running too fast, you can cut down on

its supply of substrates by dietary changes, and you can encourage its

competition by giving them what they need.

If a process is producing toxins because of a genetic problem, you can

encourage the means of processing the toxins, or you can bind them and

carry them out of the body.

If there is a blockage that is preventing something from being formed,

such as sulfate, you can supply it with an Epsom salts bath.

The general idea is that you work at the biochemical level to

compensate for problems at the genetic level.

I hope this clarifies the rationale.

Rich

>

> What I am having a problem with is that if SNPs are irregular and

> therefore a genetic componet is probable as a cause of CFS, are

> herbs and vitamins per the Yasko protocol going to be enough to

> restore us to good health? Seems like it will take a bit more than

> that. However, I haven't followed the Yasko treatment protocol

> closely, and will give it more study per Rich's recent response to

> my related question which I greatly appreciate.

>

> Mike C

[Guest guest]

Hi, a.

I think the key thing here is that these treatments are tailored to

the particular genetic variations, and the timing and combinations are

selected to achieve certain biochemical goals along the way, which are

monitored using spot urine testing. In other words, there's a little

more understanding and finesse involved that just gobbling a bunch of

pills out of a bunch of bottles. But you're right. Time will tell if

it works for PWCs.

Rich

However, when I see the

> treatments they look a lot like treatments many have been trying for

> over a decade.

>

> a

>

[Guest guest]

" rvankonynen " <richvank@...> wrote:

>

> Hi, .

> I think you may be right about at least a lot of the cases

> of " original CFS, " as you put it, i.e. the epidemic cases. But

there are many sporadic cases within the fold, also.

> Rich

I don't quite understand the point of making any distinction.

The vast majority of cases developed in isolation from others, over a

period of a year. So I guess that except for the few " clusters " ,

almost all of us could be considered " sporadic " cases.

Same illness, though.

And since it WAS the same illness, the clusters are evidence that it

has the capacity to manifest in clusters of unrelated people, which

is something that genetic illnesses are not known to do.

So I guess autism and CFS do share a pretty spectacular similarity:

They are both increasing at a rate that can not possibly be explained

by an increase in inherited genetic flaws.

People with these characteristics lack the capacity to reproduce

their genes at a rate that could match the increased prevalence.

-