Re: COMT: a connecting link?

[Guest guest]

Rich~

You mean there is no feedback mechanism to slow down the production of

adrenalin, ie is that says it is building up, stop producing?

Adrienne

COMT: a connecting link?

Hi, all.

I would like to hear from PWCs who have had the Genovations

tests at Great Smokies Lab, and have found that the gene for

their COMT (catecholamine O methyl transferase) enzyme has a

non-normal variant, particularly a slow variant. I have heard from

a couple so far, and the results sound interesting.

I suspect that a slow COMT could be a possible link between a

history prior to CFS onset of high long-term stress, and the

development of glutathione depletion and a state of oxidative

stress. If so, this would introduce a genetic component to the

glutathione-depletion pathogenesis hypothesis, and may explain

why some people under high long-term stress develop CFS,

while most others don't. There is evidence in general that

genetic variations are involved in CFS, but so far we haven't

known what specific genes are involved.

Here's how the story would go: The person is subjected to

some combination of a variety of stressors over a long period of

time. One of the effects of this is that the hypothalamus

stimulates the sympathetic nervous system to signal the

medullas of the adrenal glands to secrete adrenalin

(epinephrine) at elevated rates over a long time.

Normally, the adrenalin is broken down primarily by a pathway

that makes use of the enzyme COMT. However, if the person

has a slow or non-functioning version of this enzyme, then the

adrenalin will build up in concentration and will be broken down

by alternate pathways.

[Guest guest]

Hello Rich,

I did the genovations detox profile. Under COMT, both chromosomes

carry teh genetic variation.

I will send another email with my other variations. May be you could

provide some insight on it.

Thanks,

Gayathri.

> Hi, all.

>

> I would like to hear from PWCs who have had the Genovations

> tests at Great Smokies Lab, and have found that the gene for

> their COMT (catecholamine O methyl transferase) enzyme has a

> non-normal variant, particularly a slow variant. I have heard

from

> a couple so far, and the results sound interesting.

>

[Guest guest]

Hi Rich and others.

Regarding the genovations test.

Im reporting the tests done by a family member.

PHASE I Detoxification:

Cytochrome P-450

Gene CYP1B1 there was a polymorphism.

Gene CYP2C19 there was a polymorphism.

Genes CYP1A1, CYP2A6, CYP2C9, , CYP2D6, CYP2E1, CYP3A4 were

normal.

PHASE II:

Methylation:

COMT - both chromosome carry the genetic variation.

Acetylation:

Slow metabolizer polymorphism

Gene NAT2 -l114t both chromosome carry the genetic

variation.

FAST METABOLIZER POLYMORPHISM

Gene NAT2 -k268R - both chromosomes carry the genetic variation.

Glutathione conjugation:

Gene GSTM1 -1p13.3 carries a NULL allele meaning no gene present on

either chromosome.

Gene GSTP1 -l104V one of the chromosomes carries a genetic variation.

Gene GSTP1 -A113V no genetic variation

Oxidative protection:

Gene SOD1 -G93A no genetic variation

Gene SOD1 -A4V no genetic variation

Gene SOD2 -A16V One of the chromosome carries a genetic variation.

To Gayathri:

The similarities on our tests:

Cytochrome CYP 1B1

COMT: both chromsomes carries the genetic variation,

Acetylation NAT 2: for slow metabolizer , both ++

and Acetylation NAT 2: for fast metabolizer, both ++

Interesting as always Rich , thanks !

Per

[Guest guest]

Adrienne,

With short-term stress, when the stressful situation stops, the

adrenalin secretion goes back down. In CFS, there often seems to be

a history of long-term stress. In this case, the adrenalin

secretion continues. By long-term, I mean weeks to months or

longer, such as in unresolved conflict situations.

Rich

> Rich~

> You mean there is no feedback mechanism to slow down the

production of adrenalin, ie is that says it is building up, stop

producing?

> Adrienne

[Guest guest]

On the Genovations Dexto Profile, my results were:

COMT ++ Liver/gut

Slow Metabolizer Polymorphs

NAT2 ++ Liver/gut

Fast Metabolizer Polymorphs

NAT2 ++ Liver/gut

Glutathione Conjugation

GSTM1 NULL Liver/kidney

Oxidative Protection

SOD2 + - Mitochondria

To my (faulty) memory the test cost around $250 bucks U.S..

You can see I took a double whammy in the COMT, and I was under a lot

of stress at the time I came down with CFS.

Dr. Cheney said my NULL GSTM1 gene might simply be in a different

location than where they were looking.

He seemed to think my gravest concern was with the SOD2 + - variation.

He suggested that was where the perioxnitrite comes from. The

diminished amount of Super Oxy Dimutase allows all kinds of bad

things to happen with free radicals. He said high dose CoQ10 and

hydroxycobalamin were the treatment. Unfortunately, I cannot

tolerate CoQ10.

Genetics are interesting.

Zippy

[Guest guest]

Sorry, I neglected to mention my Cytochrome P-450's

I won the booby prize here with more SNP's than anybody in his

practice.

I had enzyme SNP's on:

CYP1B1

CYP2C9

CYP2C19

CYP2E1

In other words, I hit four for eight. (

Zippy

[Guest guest]

To the best of my

ability to determine,

here is what we

have so far:

------------------

Zippy Genes:

CYP1B1

CYP2C9

CYP2C19

CYP2E1

COMT V158M + +

NAT2 l114T + +

NAT2 K268R + +

GSTM1 1p13.3 NULL

SOD2 A16V + -

----------------------------------------

Carol Genes:

CYP1B1

CYP2C19

COMT V158M + +

NAT2 l114t + -

NAT2 K268R + -

GSTM1 1p13.3 NULL

SOD2 A16V + -

--------------------------------------

Per h Genes:

CYP1B1

CYP2C19

COMT + +

NAT2 l114T + +

GSTM1 1p13.3 NULL

GSTP1 l104V + -

SOD2 A16V + -

--------------------------------------

Gayathri Genes:

CYP1B1

COMT + +

NAT2 L114T + +

NAT2 K268R + +

---------------------------------------

Out of a study group of four

That would be:

100% CY1B1

75% CY2C19

100% COMT + +

100% NAT L114T + +, or + -

75% NAT2 K268R + +, or + -

75% GSTM1 1p13.3 NULL

75% SOD2 A16V + -

----------------------------------------

Interesting...,

Zippy

[Guest guest]

Hi Rich,

Stepping out from lurking mode to give you my Genovations Detox results as I

seem to be the only one without this genetic variation, COMT that you are asking

about.

Methylation:

COMT neither chromosome carries the genetic variation

Acetylation: slow metabolizer polymorphism

NAT2 l114T one chromsome carries the genetic variation

NAT2 R197Q one chromosome carries the genetic variation

The remaining 4 have no genetic variation

Acetylation " fast metabolizer polymorphism

NAT2 K268R one chromosome carries the genetic variation

Glutathione Conjugation

GSTM1 1p13.3 is IND, meaning their test indicates the gene is present, but they

are not able to determine whether the gene is present on one or both

chromosomes. I guess if they can't find it, they can't determine whether it is a

variant or not, if I interpret the words " our test indicates the gene is

present " correctly.

The remaining two genes have no genetic variation.

Oxidative Protection

Of the three genes looked at here, none carries the genetic variation.

I find it interesting that Carol's MIA gene is the same one they can't " find "

according to my tests, but they know it is present somewhere, although whether

normal or variant they can't determine because they can't find it. (Have I

interpreted their commentary correctly?)

Donna in NC

PS - my life has always been one of high stress, from taking care of a sick

mother and my siblings since I was a young child, to high stress, long hour

jobs, long and strenuous workouts three times a week at least,and unfortunately,

a high stress personal life, and very little sleep even as a child.

[Guest guest]

, other Aussies

I'm not sure if these are the same but the GSDL Genovations tests, are

available to Australians through FIT www.fit.net.au. The three available

are Cardio Genomic Profile, Osteo Genomic Profile and Immuno Genomic Profile

(Identifies genetic risk for defects in immune defense and upregulated

inflammatory response). Not cheap of course, the latter being AUD$374.

BTW Thanks Rich for your 5-HTP/Vit C feedback.

Caleb

--------------

From: " Light " <jligh000@...>

Subject: Re: COMT: a connecting link? - Rich

[sNIP]

I would be extremely interested in having these tests done, however,

living in Australia makes it impossible i think?