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23andme methylation SNPs again

Messages
11
Location
Germany
Good evening.
Today I just received my 23andme results and I want to see if I should do changes to my methylation protocol based on what the SNPs imply. At the moment I'm on the standard (methylmate b and hydroxob12 drops etc.) protocol, but it didn't do anything in 3 months.

Table: http://img9.myimg.de/methana15d4e2.jpg

Really complicated stuff, but I tried to note some important imformation from various sources.
--------------------------------------------------------------------------------------------------

Gene | Mutation | Genotype | Reaction | up/downregulation? | effect

CBS | C699T | -/- | homocysteine -> cystathionine | normal | no mutation. Lower potential for ammonia detoxification issues.
CBS | A360A| +/- | homocysteine -> cystathionine | up | ("C699T light") Homocysteine and all of the upstream methyl cycle precursors will be “pulled down the CBS drain” to produce toxic levels of cystathionine metabolites. Co-Q10 and Carnitine generation will fall off due to impaired methylation, and ATP levels fall, robbing you of energy.
CBS | N212 N | -/- ------------

COMT | V158M | +/- | Dopamine -> homovanillic acid | down | a lot of free methyl groups floating around. risk of overdriving with ch3 groups
COMT | H62H | +/- same
COMT | -61 P199P | -/- same (normal down)

MTHFR | C667T | +/- | THF -> 5-methyl-THF | down | folic acid doesn't reduce homocysteine level, 5-methyl-THF does
MTHFR | A1298C | +/- | BH2 -> BH4 | down | mood swings, impaired serotonin dopamine balance
MTHFR | 03 P39P | +/- | ---------------------

MTR | A2756G | -/- | 5-methyl-THF + homocysteine -> methionine + THF | normal

MTRR | A66G | +/+ | methyl-b12 formation | down | MTR doesn't get enough mb12. high homocysteine. this defect NEEDS MB12 (but considering COMT +/- status it's complicated)
MTRR | H595Y | -/- | ------------
MTRR | K350A | -/- | -----------
MTRR | R415T | -/- | ---------
MTRR | A664A | -/- | ----------
MTRR | S275T | N/A ------------

VDR | Taq | -/- | -------- dunno, confusing literature. this Taq/Bsm constellation is probably okay ------
VDR | Bsm | +/- | -----------
VDR Fok 1 | N/A |

NOS | 3 D298E | N/A

ACE | Del 16 | N/A

SHMT1 | C1420T | +/- | dunno, somehow not important

BHMT-01 | N/A
BHMT-02 | +/- | homocysteine -> methionine | down | high homocysteine, another methionine production way blocked
BHMT-04 | +/- | same
BHMT-08 | +/+ | same

MAO A | R297R | -/- -------------------

ACAT1-02 -/- -----------

ACHY-01 -/- -------------
ACHY-02 -/- ------------
ACHY-19 -/- ------------

SUOX | S370S | N/A

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

So... when the things I noted are correct, I have multiple blocks/abnormalities in the cycle and should switch to methylb12 (bc MTRR), but carefully because of my COMT status? Also my homocysteine must be very high. But it get's drained by CBS, producing toxic levels of cystathione...
Does anyone have a similar constellation?

I'd really appreciate it if anyone could identify mistakes, add information or just comment. As the layman I am I can't trust myself, so please feel free to.

greetings,
-baboon
 

maddietod

Senior Member
Messages
2,856
Baboon, I've just sent for a 23andme kit. How did you relate your findings to CFS? Do you have any links I could use to interpret my results?

Madie
 
Messages
11
Location
Germany
I can't be sure wether this really relates to CFS. Before my flu/mono 8 years ago I was completely healthy and genes don't change over time. The Light's gene expression study* shows some altered expression after excercise in specific genes of CFS patients, but the only one overlapping is COMT. Gene expression is to some extent regulated by methylation. In the specific case of COMT it could be a loop leading to depression and more because of dopamine "loss".
So these SNPs may support the prolongation of the illness, the chronic manifestation. According to the hypothesis this started when the flu/mono in my case depleted glutathione so much that some switch was flipped. Maybe an important change to one or more metabolism pathways (i.e. folate/methylation cycle), kind of switched to CFS homeostasis or something.
Now if the methylcobalamin kicks in real hard, I'll definitely give this approach another chance.

In general you should read up richvank's GD-MCB hypothesis and always try to look at the metabolism-pics.
http://geneticgenie.org/methylation-analysis/ < for the conversion from 23andme raw txt to this nice table of methylation-related SNPs
http://www.heartfixer.com/AMRI-Nutrigenomics.htm < I mostly looked at this page
http://www.dramyyasko.com/wp-content/files_flutter/1327512160_9_1_1_8_pdf_02_file.pdf < start at page 124 "How to Read the Nutrigenomic Test"
http://www.vsan.org/rok-az/methylation/Genetic_Analysis_Report_summary_sheet_1.pdf < somewhat incomplete but easy to understand

* http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02405.x/full
 

roxie60

Senior Member
Messages
1,791
Location
Central Illinois, USA
Good evening.
Today I just received my 23andme results and I want to see if I should do changes to my methylation protocol based on what the SNPs imply. At the moment I'm on the standard (methylmate b and hydroxob12 drops etc.) protocol, but it didn't do anything in 3 months.

Table: http://img9.myimg.de/methana15d4e2.jpg

Really complicated stuff, but I tried to note some important imformation from various sources.
--------------------------------------------------------------------------------------------------

Gene | Mutation | Genotype | Reaction | up/downregulation? | effect

CBS | C699T | -/- | homocysteine -> cystathionine | normal | no mutation. Lower potential for ammonia detoxification issues.
CBS | A360A| +/- | homocysteine -> cystathionine | up | ("C699T light") Homocysteine and all of the upstream methyl cycle precursors will be “pulled down the CBS drain” to produce toxic levels of cystathionine metabolites. Co-Q10 and Carnitine generation will fall off due to impaired methylation, and ATP levels fall, robbing you of energy.
CBS | N212 N | -/- ------------

COMT | V158M | +/- | Dopamine -> homovanillic acid | down | a lot of free methyl groups floating around. risk of overdriving with ch3 groups
COMT | H62H | +/- same
COMT | -61 P199P | -/- same (normal down)

MTHFR | C667T | +/- | THF -> 5-methyl-THF | down | folic acid doesn't reduce homocysteine level, 5-methyl-THF does
MTHFR | A1298C | +/- | BH2 -> BH4 | down | mood swings, impaired serotonin dopamine balance
MTHFR | 03 P39P | +/- | ---------------------

MTR | A2756G | -/- | 5-methyl-THF + homocysteine -> methionine + THF | normal

MTRR | A66G | +/+ | methyl-b12 formation | down | MTR doesn't get enough mb12. high homocysteine. this defect NEEDS MB12 (but considering COMT +/- status it's complicated)
MTRR | H595Y | -/- | ------------
MTRR | K350A | -/- | -----------
MTRR | R415T | -/- | ---------
MTRR | A664A | -/- | ----------
MTRR | S275T | N/A ------------

VDR | Taq | -/- | -------- dunno, confusing literature. this Taq/Bsm constellation is probably okay ------
VDR | Bsm | +/- | -----------
VDR Fok 1 | N/A |

NOS | 3 D298E | N/A

ACE | Del 16 | N/A

SHMT1 | C1420T | +/- | dunno, somehow not important

BHMT-01 | N/A
BHMT-02 | +/- | homocysteine -> methionine | down | high homocysteine, another methionine production way blocked
BHMT-04 | +/- | same
BHMT-08 | +/+ | same

MAO A | R297R | -/- -------------------

ACAT1-02 -/- -----------

ACHY-01 -/- -------------
ACHY-02 -/- ------------
ACHY-19 -/- ------------

SUOX | S370S | N/A

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

So... when the things I noted are correct, I have multiple blocks/abnormalities in the cycle and should switch to methylb12 (bc MTRR), but carefully because of my COMT status? Also my homocysteine must be very high. But it get's drained by CBS, producing toxic levels of cystathione...
Does anyone have a similar constellation?

I'd really appreciate it if anyone could identify mistakes, add information or just comment. As the layman I am I can't trust myself, so please feel free to.

greetings,
-baboon

Curious baboon where you found information regarding conclusions/comments ('effect') you made, based on reading various sources like Yasko and hartfixer or some other source?
 
Messages
11
Location
Germany
Curious baboon where you found information regarding conclusions/comments ('effect') you made, based on reading various sources like Yasko and hartfixer or some other source?
I've studied biochemistry for 2 years, but due to cancer and ME I had to give up. So I have a very basic knowledge of how enzymes, genes etc. work. I came up myself with some of the conclusions/comments, others were just noted from the links. But to be honest, I don't trust Amy Yasko's work that much, or rather what's been sold at her holisticheal shop.
Those RNA products... Even if the "right" RNA is in there, how the hell will it survive in some water solution without being frozen at real low temperatures. Also, wouldn't it get destroyed in the saliva? Anyways, I wouldn't be too surprised if most of this was bullshit. And if this is the case, what I wrote earlier will be too. But I'll still try methylb12 and/or adenosylb12, because it's cheap and there are many positive reports from many different people all over the world.
I don't think it's just the placebo effect.
 

roxie60

Senior Member
Messages
1,791
Location
Central Illinois, USA
i.r. baboon could you please clarify one of your comments
'COMT | -61 P199P | -/- same (normal down)'

Are you saying the COMT P199P 'normal' results in 'down' regulation?
 
Messages
11
Location
Germany
No, it's a mistake.
No mutation = enzyme working at normal speed.
Apart from that, there is no real "normal". It's just like "The majority of people have version xy of the gene. The enzyme it codes is working at speed x". Other versions/mutations of the gene may cause the enzyme to work at a different speed. It's a question of what you define as normal.

From Heartfixer: "A third, and less frequently encountered COMT abnormality, COMT 61, is a down regulation defect. Individuals (+) for COMT 61 breakdown dopamine quite rapidly and are at greatest need for methyl donors."

This statement is contradictory.
If having this mutation means COMT is working slower (downregulation), then dopamine is broken down LESS rapidly.
 

Symptomatic

Senior Member
Messages
197
Those RNA products... Even if the "right" RNA is in there, how the hell will it survive in some water solution without being frozen at real low temperatures. Also, wouldn't it get destroyed in the saliva?.

Not defending Yasko or her products, but there are modified types of RNA (e.g. 2'-O-Methyl, 2'-methoxyethyl, RNA with phosphorothioate linkages, etc.) that are significantly more stable than unmodified RNA. Many companies are working with these types of modified RNA when trying to develop RNA therapeutics.