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23andme analysis and treatment (COMT/VDR/MAO)

Messages
20
I've been doing a fair amount of research around the COMT V158M +/+ (also known as AA or Met/Met) result, and it seems that the COMT SNP is a pretty cast-iron diagnosis, not an indication of inclination..

The many scientific studies out there that cover the COMT V158M (also known as rs4680 or Val158Met) polymorphism include it because it affects the treatment for Parkinson's and Schizophrenia (it's all about money when it comes to studies being done or not).

If you give Parkinson's and Schizophrenia drugs to people with the polymorphism, they will react badly to it. That's because the drugs LOWER COMT activity, which for people whose COMT activity is already too low, will mean their dopamine, epinephrine, and norepinephrine levels will go through the roof.

"It is an extremely well-studied polymorphism with 165 papers referencing it on pubmed as of 2012."

"In this case that single amino acid change from valine to methionine [the polymorphism] has a dramatic impact on the protein’s function."

"The Val158Met polymorphism in the COMT gene leads to an amino-acid substitution (valine (Val) to methionine (Met)) and results in the Met/Met variant showing 40% less enzymatic activity than the Val/Val."
from http://www.nature.com/npp/journal/v33/n13/full/npp200882a.html

Other links:

https://neuroamer.wordpress.com/201...-one-gene-comt-catechol-o-methyl-transferase/

And http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182110/pdf/AJHGv75p807.pdf

Am I right here? Or barking up the wrong tree?
 
Messages
20
I'd suggest that you discuss your symptoms with your doctor.

I have spoken to many doctors about this over the past 10 years, including NHS GPs, Endocrinologists, GI Docs, Nutritionalists and a Neurologist.. Nobody has been able to get to the root of the issue, treating symptoms rather than causes, meaning I'm having to (try to) work everything out my self.
 
Messages
20
What do you mean by that?

I mean that the COMT V158M +/+ polymorphism shows that your COMT activity is significantly lower than for people without the polymorphism.

It's a definite indication of underperforming COMT activity. It's not a flag saying that you're statistically more likely to suffer from a certain condition.

"A homozygous polymorphism means you will use two methionine molecules and this is known as Met/Met. Genetic Genie reports this as AA. If you have this version, your catechol-o-methyl transferase will be only one quarter as effective as a person with the Val/Val genotype."
From this useful roundup: http://ihateticks.me/2014/11/17/the-comt-polymorphism/

There are lots of scientific studies out there that cover this. Such as:

http://www.ncbi.nlm.nih.gov/pubmed/25560469
http://www.ncbi.nlm.nih.gov/pubmed/25218601
http://www.ncbi.nlm.nih.gov/pubmed/25238062
http://www.ncbi.nlm.nih.gov/pubmed/25753458

That's how I understand it anyway :)
 

Gondwanaland

Senior Member
Messages
5,092
What do you mean by that?
I think it means that if one is +/+COMT troubles with neurotansmitter breakdown will be present sooner or later.

For my husband for instance, he always had a tendency to poor management of stress, but after 37 years old the situation became dramatic with nerve damage. I think it has something to do with toxic load (esp. prescription medicines) impairing neurotransmitter breakdown even more.
 
Messages
15,786
I mean that the COMT V158M +/+ polymorphism shows that your COMT activity is significantly lower than for people without the polymorphism.

It's a definite indication of underperforming COMT activity. It's not a flag saying that you're statistically more likely to suffer from a certain condition.
It's definitely not diagnostic ... it's an extremely common variation, and generally doesn't result in any problems. Some mildly increased risks are associated with it, but so are some mildly decreased risks.
 
Messages
20
It's definitely not diagnostic

I'm not talking about symptoms or problems. I'm talking about the impact of the altered gene. It lowers the activity of the COMT enzyme.

"The Val158Met polymorphism in the COMT gene leads to an amino-acid substitution (valine (Val) to methionine (Met)) and results in the Met/Met variant showing 40% less enzymatic activity than the Val/Val."
from http://www.nature.com/npp/journal/v33/n13/full/npp200882a.html

Is that not true in your opinion?
 
Messages
15,786
I'm not talking about symptoms or problems. I'm talking about the impact of the altered gene. It lowers the activity of the COMT enzyme.
Sure, it impacts gene function. But there's no indication that the high prevalence of variable function in that gene is particularly problematic. Just some mild associations with various personality and psychological traits in psych research, which tends to lack scientific rigor.
 
Messages
20
Sure, it impacts gene function. But there's no indication that the high prevalence of variable function in that gene is particularly problematic.

I'm not saying that it is a problem for everyone, simply that the polymorphism indicates a definite, physical fact - that the COMT enzyme is going to be performing more slowly.

To know that a main inhibitor of adrenaline and dopamine isn't working very well is a very useful bit of information for those of us who have been suffering from escalating symptoms of an excess of adrenaline and dopamine, and have ruled most other causes out.

To reiterate - I'm not saying COMT polymorphisms cause problems with everyone. But they do affect everyone who has them to some degree, whether they are aware of it or not - some positive, some negative. It all depends on other variables (accompanying health conditions, lifestyle, life).
 

TheChosenOne

Senior Member
Messages
209
Just some mild associations
There are indeed modest associations. These can be aggravated by methylsupplements, so this is of particular importance for individuals who are adressing methylation which makes treatment much more difficult, especially if there is a combination of COMT mutations or if that person has anxiety/mood swings/bipolar.
 
Messages
1
Keep at it twincity and all you folks trying to improve your health. Like you I have been throwing myself against the vast amounts of information hoping to make sense of something,trying to keep up with the research and relate it to my symptoms. I know I will never give up because that is just not an option for me( double COMT homo =lots of dopamine which keeps me on task albeit always stressed?) gut healing started for me when I gave up grain and I lost a heap of symptoms. For me the genetics point in a general direction and I jump in and swim around that area to see what might be part of the problem-try some changes and see what happens! Just feeling you are doing something however small is a great feeling.