Re: SNPs in our group compared to publications

[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.

>

Hi Rich

Can you just remind me which is the SNP that stops the enzyme involved

in the conversion of folic acid to its active form. I think I have

finally understood why one might not get benefits from taking folic

acid to try and help the methylation cycle but its quite difficult to

get folinic acid here in the UK. All of the main manufacturers of

supplements here in the UK just use folic acid however I notice that

Kirkmans do TMG plus B12 and folinic acid so I have just ordered a pot

and hope that this will get the methylation cycle working normally.

Many thanks

Pam

[Guest guest]

Rich,

Thanks for all the info. Unfortunately, I really have not reacted

either positively or negatively to anything I have ever tried, and I

have tried many things. The only thing I have responded to was thyroid

supplementation, but as my doctor kept increasing the dosage, I

crashed and have not been able to try it since.

Thanks though,

Chris

> >

> > 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, Pam.

There is more than one possible hang-up in the folate system. It is

possible to have SNPs in the MTHFR enzyme (methylene

tetrahydrofolate reductase). A SNP in the part that involves the

forward direction of the MTHFR reaction will hinder the production

of 5-methyl tetrahydrofolate. If there is a SNP in MTR or MTRR

(methionine synthase or methionine synthase reductase) then there

could be problem in producing tetrahydrofolate.

Jon Pangborn recommends folinic acid (5-formyl tetrahydrofolate) as

the most versatile form for supplementation. Dr. Yasko uses in

addition FolaPro (5-methyl tetrahydrofolate) emphasizing that a SNP

in the forward direction of the MTHFR reaction can prevent folinic

from being used to make 5-methyl THF, which is needed by the MTR

enzyme.

We don't know which SNPs you have, I guess. I hope the folinic does

the job for you.

Rich

> Hi Rich

>

> Can you just remind me which is the SNP that stops the enzyme

involved

> in the conversion of folic acid to its active form. I think I

have

> finally understood why one might not get benefits from taking

folic

> acid to try and help the methylation cycle but its quite difficult

to

> get folinic acid here in the UK. All of the main manufacturers of

> supplements here in the UK just use folic acid however I notice

that

> Kirkmans do TMG plus B12 and folinic acid so I have just ordered a

pot

> and hope that this will get the methylation cycle working normally.

>

> Many thanks

>

> Pam

>

[Guest guest]

Hi Rich,

thanks for putting this together. What are the concequences of the ACE double

deletion (incluidng what are the effects on sodium/potassium metabolism?) and

how can it be compensated for?

Blake

SNPs in our group compared to publications

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]

> 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.

Hi - FWIW, you are referring to these silent polymorphisms using two

different naming conventions. To be consistent, you should refer to

A360A as C108OT.

Secondly, regarding the distribution of the different genotypes in the

general population, here's information from the 2003 study: 699CC,

699CT, 1080CC, and 1080CT all occur between 40% and 50% in the general

population. Only 699TT and 1080TT aren't common:

Genotype Patients % Controls % Fasting tHcy Postload tHcy Change

tHcy

699CC 76 (40.0) 156 (42.9) 13.9 40.0 25.1

699CT 87 (45.8) 158 (43.4) 13.5 39.6 25.5

699TT 27 (14.2) 50 (13.7) 14.2 40.0 25.1

1080CC 93 (49.2) 150 (40.4) 14.0 40.6 25.9

1080CT 70 (37.0) 164 (44.2) 13.6 39.1 24.9

1080TT 26 (13.8) 57 (15.4) 13.5 39.7 24.4

In this study, no difference in homocysteine levels were found in the

different groups, i.e. no proof of CBS upregulation was found for any of

the different genotypes, even the less common ones.

It was only in the 2000 study that a decrease in homocysteine was seen

in 1080TT and 699TT, and somewhat in 699CT. The reduction in 1080TT was

only significant though, if other polymorphisms were eliminated.

Why these studies differ is unknown. However, while the 2000 study had

about twice as many people, 3/4 of the people in that 2000 study had

confirmed artery disease, and most of the other 1/4 people were being

evaluated for cardiovascular disease. On the other hand, in the 2003

study, only 1/3 of the people were patients, while the other 2/3 were

people from 2 different GP doctors. Thus, the 2003 study represented a

more diverse population. (Also, the 2003 study was conducted in a

different country.)

In any event, if you can show that a significant amount of people with

CFS either have genotypes 1080TT or especially 699TT, then it might be

significant, depending upon which of the above studies that you believe

in. - Mark

..

[Guest guest]

Mark, is it possible to provide references for these studies? I would

appreciate. Thanx./Jill

> > 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.

>

> Hi - FWIW, you are referring to these silent polymorphisms using two

> different naming conventions. To be consistent, you should refer to

> A360A as C108OT.

>

> Secondly, regarding the distribution of the different genotypes in the

> general population, here's information from the 2003 study: 699CC,

> 699CT, 1080CC, and 1080CT all occur between 40% and 50% in the general

> population. Only 699TT and 1080TT aren't common:

>

> Genotype Patients % Controls % Fasting tHcy Postload tHcy Change

> tHcy

> 699CC 76 (40.0) 156 (42.9) 13.9 40.0 25.1

> 699CT 87 (45.8) 158 (43.4) 13.5 39.6 25.5

> 699TT 27 (14.2) 50 (13.7) 14.2 40.0 25.1

>

> 1080CC 93 (49.2) 150 (40.4) 14.0 40.6 25.9

> 1080CT 70 (37.0) 164 (44.2) 13.6 39.1 24.9

> 1080TT 26 (13.8) 57 (15.4) 13.5 39.7 24.4

>

> In this study, no difference in homocysteine levels were found in the

> different groups, i.e. no proof of CBS upregulation was found for any of

> the different genotypes, even the less common ones.

>

> It was only in the 2000 study that a decrease in homocysteine was seen

> in 1080TT and 699TT, and somewhat in 699CT. The reduction in 1080TT was

> only significant though, if other polymorphisms were eliminated.

>

> Why these studies differ is unknown. However, while the 2000 study had

> about twice as many people, 3/4 of the people in that 2000 study had

> confirmed artery disease, and most of the other 1/4 people were being

> evaluated for cardiovascular disease. On the other hand, in the 2003

> study, only 1/3 of the people were patients, while the other 2/3 were

> people from 2 different GP doctors. Thus, the 2003 study represented a

> more diverse population. (Also, the 2003 study was conducted in a

> different country.)

>

> In any event, if you can show that a significant amount of people with

> CFS either have genotypes 1080TT or especially 699TT, then it might be

> significant, depending upon which of the above studies that you believe

> in. - Mark

>

>

> .

>

>

>

[Guest guest]

Hi, Blake.

Apparently there can be a lot of consequences to this SNP. Someone

from another group referred me to a paper, which I've just started

to read:

http://www.genomed.com/pdf/ACE_vertebrate_pathophysiology.pdf

I can't vouch for this company or what they are recommending, but

they discuss the use of ACE inhibitor drugs for a variety of

conditions.

I don't currently know of a non-drug approach that can completely

deal with this overactive SNP. I'm still on the learning curve

about this, but it sounds as though this SNP can be important.

Rich

>

> Hi Rich,

>

> thanks for putting this together. What are the concequences of the

ACE double deletion (incluidng what are the effects on

sodium/potassium metabolism?) and how can it be compensated for?

>

> Blake

[Guest guest]

Hi, Mark.

> > 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.

>

> Hi - FWIW, you are referring to these silent polymorphisms using

two

> different naming conventions. To be consistent, you should refer

to

> A360A as C108OT.

***You're right. Thank you.

>

> Secondly, regarding the distribution of the different genotypes in

the

> general population, here's information from the 2003 study: 699CC,

> 699CT, 1080CC, and 1080CT all occur between 40% and 50% in the

general

> population. Only 699TT and 1080TT aren't common:

>

> Genotype Patients % Controls % Fasting tHcy Postload tHcy

Change

> tHcy

> 699CC 76 (40.0) 156 (42.9) 13.9 40.0

25.1

> 699CT 87 (45.8) 158 (43.4) 13.5 39.6

25.5

> 699TT 27 (14.2) 50 (13.7) 14.2 40.0

25.1

>

> 1080CC 93 (49.2) 150 (40.4) 14.0 40.6

25.9

> 1080CT 70 (37.0) 164 (44.2) 13.6 39.1

24.9

> 1080TT 26 (13.8) 57 (15.4) 13.5 39.7

24.4

>

> In this study, no difference in homocysteine levels were found in

the

> different groups, i.e. no proof of CBS upregulation was found for

any of

> the different genotypes, even the less common ones.

>

> It was only in the 2000 study that a decrease in homocysteine was

seen

> in 1080TT and 699TT, and somewhat in 699CT. The reduction in

1080TT was

> only significant though, if other polymorphisms were eliminated.

>

> Why these studies differ is unknown. However, while the 2000

study had

> about twice as many people, 3/4 of the people in that 2000 study

had

> confirmed artery disease, and most of the other 1/4 people were

being

> evaluated for cardiovascular disease. On the other hand, in the

2003

> study, only 1/3 of the people were patients, while the other 2/3

were

> people from 2 different GP doctors. Thus, the 2003 study

represented a

> more diverse population. (Also, the 2003 study was conducted in a

> different country.)

>

> In any event, if you can show that a significant amount of people

with

> CFS either have genotypes 1080TT or especially 699TT, then it

might be

> significant, depending upon which of the above studies that you

believe

> in. - Mark

>

***Thanks for this information, Mark. In regard to homocysteine

decrease, that may not be a very clearcut indicator of CBS

upregulation because of the other two pathways for homocysteine,

i.e. methionine synthase and the betaine-induced pathway.

Furthermore, there seem to be some rather complex feedbacks that

occur in the methylation cycle, that affect the homocysteine level.

***Jill also gave me some comments, and she, too, emphasized

that the CBS SNPs are not well-characterized in the published

literature. Her new paper cites some references for the general

population frequencies of the SNPs she studied for autism, so

between what you and she have given me, I should be able to do a

better comparison job if I update this in the future.

***I suspect that Amy Yasko is going on the basis of unpublished

results she has from looking at SNPs and biochemical tests in a lot

of autistic kids when she says that these are upregulations.

***I can tell you that the one PWC I know of so far who is

homozygous for C699T has a very high cystathionine level in the

urine, so I'm convinced that it is truly an upregulation.

***Out of nine PWCs for whom I currently have these data, one is

C699T (+/+), and three are C1080T (+/+).

***Thanks very much for the comments an input.

***Rich

[Guest guest]

Hi, Mark.

> > 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.

>

> Hi - FWIW, you are referring to these silent polymorphisms using

two

> different naming conventions. To be consistent, you should refer

to

> A360A as C108OT.

***You're right. Thank you.

>

> Secondly, regarding the distribution of the different genotypes in

the

> general population, here's information from the 2003 study: 699CC,

> 699CT, 1080CC, and 1080CT all occur between 40% and 50% in the

general

> population. Only 699TT and 1080TT aren't common:

>

> Genotype Patients % Controls % Fasting tHcy Postload tHcy

Change

> tHcy

> 699CC 76 (40.0) 156 (42.9) 13.9 40.0

25.1

> 699CT 87 (45.8) 158 (43.4) 13.5 39.6

25.5

> 699TT 27 (14.2) 50 (13.7) 14.2 40.0

25.1

>

> 1080CC 93 (49.2) 150 (40.4) 14.0 40.6

25.9

> 1080CT 70 (37.0) 164 (44.2) 13.6 39.1

24.9

> 1080TT 26 (13.8) 57 (15.4) 13.5 39.7

24.4

>

> In this study, no difference in homocysteine levels were found in

the

> different groups, i.e. no proof of CBS upregulation was found for

any of

> the different genotypes, even the less common ones.

>

> It was only in the 2000 study that a decrease in homocysteine was

seen

> in 1080TT and 699TT, and somewhat in 699CT. The reduction in

1080TT was

> only significant though, if other polymorphisms were eliminated.

>

> Why these studies differ is unknown. However, while the 2000

study had

> about twice as many people, 3/4 of the people in that 2000 study

had

> confirmed artery disease, and most of the other 1/4 people were

being

> evaluated for cardiovascular disease. On the other hand, in the

2003

> study, only 1/3 of the people were patients, while the other 2/3

were

> people from 2 different GP doctors. Thus, the 2003 study

represented a

> more diverse population. (Also, the 2003 study was conducted in a

> different country.)

>

> In any event, if you can show that a significant amount of people

with

> CFS either have genotypes 1080TT or especially 699TT, then it

might be

> significant, depending upon which of the above studies that you

believe

> in. - Mark

>

***Thanks for this information, Mark. In regard to homocysteine

decrease, that may not be a very clearcut indicator of CBS

upregulation because of the other two pathways for homocysteine,

i.e. methionine synthase and the betaine-induced pathway.

Furthermore, there seem to be some rather complex feedbacks that

occur in the methylation cycle, that affect the homocysteine level.

***Jill also gave me some comments, and she, too, emphasized

that the CBS SNPs are not well-characterized in the published

literature. Her new paper cites some references for the general

population frequencies of the SNPs she studied for autism, so

between what you and she have given me, I should be able to do a

better comparison job if I update this in the future.

***I suspect that Amy Yasko is going on the basis of unpublished

results she has from looking at SNPs and biochemical tests in a lot

of autistic kids when she says that these are upregulations.

***I can tell you that the one PWC I know of so far who is

homozygous for C699T has a very high cystathionine level in the

urine, so I'm convinced that it is truly an upregulation.

***Out of nine PWCs for whom I currently have these data, one is

C699T (+/+), and three are C1080T (+/+).

***Thanks very much for the comments an input.

***Rich

[Guest guest]

Rich, now that you're back online, I'll send you my results. I have

the weaker CBS upregulation. However, I am thinking the ACE deletion

is pretty meaningful for all of us.

> > > 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.

> >

> > Hi - FWIW, you are referring to these silent polymorphisms using

> two

> > different naming conventions. To be consistent, you should refer

> to

> > A360A as C108OT.

>

> ***You're right. Thank you.

>

> >

> > Secondly, regarding the distribution of the different genotypes in

> the

> > general population, here's information from the 2003 study: 699CC,

> > 699CT, 1080CC, and 1080CT all occur between 40% and 50% in the

> general

> > population. Only 699TT and 1080TT aren't common:

> >

> > Genotype Patients % Controls % Fasting tHcy Postload tHcy

> Change

> > tHcy

> > 699CC 76 (40.0) 156 (42.9) 13.9 40.0

> 25.1

> > 699CT 87 (45.8) 158 (43.4) 13.5 39.6

> 25.5

> > 699TT 27 (14.2) 50 (13.7) 14.2 40.0

> 25.1

> >

> > 1080CC 93 (49.2) 150 (40.4) 14.0 40.6

> 25.9

> > 1080CT 70 (37.0) 164 (44.2) 13.6 39.1

> 24.9

> > 1080TT 26 (13.8) 57 (15.4) 13.5 39.7

> 24.4

> >

> > In this study, no difference in homocysteine levels were found in

> the

> > different groups, i.e. no proof of CBS upregulation was found for

> any of

> > the different genotypes, even the less common ones.

> >

> > It was only in the 2000 study that a decrease in homocysteine was

> seen

> > in 1080TT and 699TT, and somewhat in 699CT. The reduction in

> 1080TT was

> > only significant though, if other polymorphisms were eliminated.

> >

> > Why these studies differ is unknown. However, while the 2000

> study had

> > about twice as many people, 3/4 of the people in that 2000 study

> had

> > confirmed artery disease, and most of the other 1/4 people were

> being

> > evaluated for cardiovascular disease. On the other hand, in the

> 2003

> > study, only 1/3 of the people were patients, while the other 2/3

> were

> > people from 2 different GP doctors. Thus, the 2003 study

> represented a

> > more diverse population. (Also, the 2003 study was conducted in a

> > different country.)

> >

> > In any event, if you can show that a significant amount of people

> with

> > CFS either have genotypes 1080TT or especially 699TT, then it

> might be

> > significant, depending upon which of the above studies that you

> believe

> > in. - Mark

> >

>

> ***Thanks for this information, Mark. In regard to homocysteine

> decrease, that may not be a very clearcut indicator of CBS

> upregulation because of the other two pathways for homocysteine,

> i.e. methionine synthase and the betaine-induced pathway.

> Furthermore, there seem to be some rather complex feedbacks that

> occur in the methylation cycle, that affect the homocysteine level.

>

> ***Jill also gave me some comments, and she, too, emphasized

> that the CBS SNPs are not well-characterized in the published

> literature. Her new paper cites some references for the general

> population frequencies of the SNPs she studied for autism, so

> between what you and she have given me, I should be able to do a

> better comparison job if I update this in the future.

>

> ***I suspect that Amy Yasko is going on the basis of unpublished

> results she has from looking at SNPs and biochemical tests in a lot

> of autistic kids when she says that these are upregulations.

>

> ***I can tell you that the one PWC I know of so far who is

> homozygous for C699T has a very high cystathionine level in the

> urine, so I'm convinced that it is truly an upregulation.

>

> ***Out of nine PWCs for whom I currently have these data, one is

> C699T (+/+), and three are C1080T (+/+).

>

> ***Thanks very much for the comments an input.

>

> ***Rich

>

[Guest guest]

Hi All,

It would help me if we just referred to the genetic mutations in the same way

they are referred to on the genetic test. ie: A360A instead of C1080T. It would

make the process easier for people to relate to, since that is what they are

looking at on the test.

Thank you,

Janet

jill1313 <jenbooks13@...> wrote:

Rich, now that you're back online, I'll send you my results. I have

the weaker CBS upregulation. However, I am thinking the ACE deletion

is pretty meaningful for all of us.

> > > 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.

> >

> > Hi - FWIW, you are referring to these silent polymorphisms using

> two

> > different naming conventions. To be consistent, you should refer

> to

> > A360A as C108OT.

>

> ***You're right. Thank you.

>

> >

> > Secondly, regarding the distribution of the different genotypes in

> the

> > general population, here's information from the 2003 study: 699CC,

> > 699CT, 1080CC, and 1080CT all occur between 40% and 50% in the

> general

> > population. Only 699TT and 1080TT aren't common:

> >

> > Genotype Patients % Controls % Fasting tHcy Postload tHcy

> Change

> > tHcy

> > 699CC 76 (40.0) 156 (42.9) 13.9 40.0

> 25.1

> > 699CT 87 (45.8) 158 (43.4) 13.5 39.6

> 25.5

> > 699TT 27 (14.2) 50 (13.7) 14.2 40.0

> 25.1

> >

> > 1080CC 93 (49.2) 150 (40.4) 14.0 40.6

> 25.9

> > 1080CT 70 (37.0) 164 (44.2) 13.6 39.1

> 24.9

> > 1080TT 26 (13.8) 57 (15.4) 13.5 39.7

> 24.4

> >

> > In this study, no difference in homocysteine levels were found in

> the

> > different groups, i.e. no proof of CBS upregulation was found for

> any of

> > the different genotypes, even the less common ones.

> >

> > It was only in the 2000 study that a decrease in homocysteine was

> seen

> > in 1080TT and 699TT, and somewhat in 699CT. The reduction in

> 1080TT was

> > only significant though, if other polymorphisms were eliminated.

> >

> > Why these studies differ is unknown. However, while the 2000

> study had

> > about twice as many people, 3/4 of the people in that 2000 study

> had

> > confirmed artery disease, and most of the other 1/4 people were

> being

> > evaluated for cardiovascular disease. On the other hand, in the

> 2003

> > study, only 1/3 of the people were patients, while the other 2/3

> were

> > people from 2 different GP doctors. Thus, the 2003 study

> represented a

> > more diverse population. (Also, the 2003 study was conducted in a

> > different country.)

> >

> > In any event, if you can show that a significant amount of people

> with

> > CFS either have genotypes 1080TT or especially 699TT, then it

> might be

> > significant, depending upon which of the above studies that you

> believe

> > in. - Mark

> >

>

> ***Thanks for this information, Mark. In regard to homocysteine

> decrease, that may not be a very clearcut indicator of CBS

> upregulation because of the other two pathways for homocysteine,

> i.e. methionine synthase and the betaine-induced pathway.

> Furthermore, there seem to be some rather complex feedbacks that

> occur in the methylation cycle, that affect the homocysteine level.

>

> ***Jill also gave me some comments, and she, too, emphasized

> that the CBS SNPs are not well-characterized in the published

> literature. Her new paper cites some references for the general

> population frequencies of the SNPs she studied for autism, so

> between what you and she have given me, I should be able to do a

> better comparison job if I update this in the future.

>

> ***I suspect that Amy Yasko is going on the basis of unpublished

> results she has from looking at SNPs and biochemical tests in a lot

> of autistic kids when she says that these are upregulations.

>

> ***I can tell you that the one PWC I know of so far who is

> homozygous for C699T has a very high cystathionine level in the

> urine, so I'm convinced that it is truly an upregulation.

>

> ***Out of nine PWCs for whom I currently have these data, one is

> C699T (+/+), and three are C1080T (+/+).

>

> ***Thanks very much for the comments an input.

>

> ***Rich

>

[Guest guest]

>>>>the same way they are referred to on the genetic test. ie: A360A instead of

C1080T.<<<<<

How are they referred to in Scientific publications and articles, and in other

test panels and laboratories? For when people want look them up in a Search, or

hear of them in other contexts.

Maybe someone can start a glossary of standard genetic terms for the files or

post one that already exists.

Katrina

> > > > 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.

> > >

> > > Hi - FWIW, you are referring to these silent polymorphisms using

> > two

> > > different naming conventions. To be consistent, you should refer

> > to

> > > A360A as C108OT.

> >

> > ***You're right. Thank you.

> >

> > >

> > > Secondly, regarding the distribution of the different genotypes in

> > the

> > > general population, here's information from the 2003 study: 699CC,

> > > 699CT, 1080CC, and 1080CT all occur between 40% and 50% in the

> > general

> > > population. Only 699TT and 1080TT aren't common:

> > >

> > > Genotype Patients % Controls % Fasting tHcy Postload tHcy

> > Change

> > > tHcy

> > > 699CC 76 (40.0) 156 (42.9) 13.9 40.0

> > 25.1

> > > 699CT 87 (45.8) 158 (43.4) 13.5 39.6

> > 25.5

> > > 699TT 27 (14.2) 50 (13.7) 14.2 40.0

> > 25.1

> > >

> > > 1080CC 93 (49.2) 150 (40.4) 14.0 40.6

> > 25.9

> > > 1080CT 70 (37.0) 164 (44.2) 13.6 39.1

> > 24.9

> > > 1080TT 26 (13.8) 57 (15.4) 13.5 39.7

> > 24.4

> > >

> > > In this study, no difference in homocysteine levels were found in

> > the

> > > different groups, i.e. no proof of CBS upregulation was found for

> > any of

> > > the different genotypes, even the less common ones.

> > >

> > > It was only in the 2000 study that a decrease in homocysteine was

> > seen

> > > in 1080TT and 699TT, and somewhat in 699CT. The reduction in

> > 1080TT was

> > > only significant though, if other polymorphisms were eliminated.

> > >

> > > Why these studies differ is unknown. However, while the 2000

> > study had

> > > about twice as many people, 3/4 of the people in that 2000 study

> > had

> > > confirmed artery disease, and most of the other 1/4 people were

> > being

> > > evaluated for cardiovascular disease. On the other hand, in the

> > 2003

> > > study, only 1/3 of the people were patients, while the other 2/3

> > were

> > > people from 2 different GP doctors. Thus, the 2003 study

> > represented a

> > > more diverse population. (Also, the 2003 study was conducted in a

> > > different country.)

> > >

> > > In any event, if you can show that a significant amount of people

> > with

> > > CFS either have genotypes 1080TT or especially 699TT, then it

> > might be

> > > significant, depending upon which of the above studies that you

> > believe

> > > in. - Mark

> > >

> >

> > ***Thanks for this information, Mark. In regard to homocysteine

> > decrease, that may not be a very clearcut indicator of CBS

> > upregulation because of the other two pathways for homocysteine,

> > i.e. methionine synthase and the betaine-induced pathway.

> > Furthermore, there seem to be some rather complex feedbacks that

> > occur in the methylation cycle, that affect the homocysteine level.

> >

> > ***Jill also gave me some comments, and she, too, emphasized

> > that the CBS SNPs are not well-characterized in the published

> > literature. Her new paper cites some references for the general

> > population frequencies of the SNPs she studied for autism, so

> > between what you and she have given me, I should be able to do a

> > better comparison job if I update this in the future.

> >

> > ***I suspect that Amy Yasko is going on the basis of unpublished

> > results she has from looking at SNPs and biochemical tests in a lot

> > of autistic kids when she says that these are upregulations.

> >

> > ***I can tell you that the one PWC I know of so far who is

> > homozygous for C699T has a very high cystathionine level in the

> > urine, so I'm convinced that it is truly an upregulation.

> >

> > ***Out of nine PWCs for whom I currently have these data, one is

> > C699T (+/+), and three are C1080T (+/+).

> >

> > ***Thanks very much for the comments an input.

> >

> > ***Rich

> >

>

>

>

>

>

>

>

[Guest guest]

Hi, Janet and Katrina.

Maybe I'll just refer to them both ways, i.e. the nucleotide

designation and the amino acid designation.

Rich

> >

> > Hi All,

> >

> > It would help me if we just referred to the genetic mutations

in the same way they are referred to on the genetic test. ie: A360A

instead of C1080T. It would make the process easier for people to

relate to, since that is what they are looking at on the test.

> >

> > Thank you,

> >

> > Janet

[Guest guest]

Hi, Jill.

O.K.

I may be on and off, but I do try to read the posts. I just don't

always have time to answer all of the ones directed to me,

especially if I have to study to answer them.

Yes, I'm getting interested in the ACE double deletion, too.

Rich

>

>

> Rich, now that you're back online, I'll send you my results. I have

> the weaker CBS upregulation. However, I am thinking the ACE

deletion

> is pretty meaningful for all of us.