News & Views on Systemic Body Odor and Halitosis such as trimethylaminuria TMAU. If you have fecal odors or bowel odors it may be metabolic/systemic

16 March 2017

Nicotine and common FMO3 variant E308G

New paper looking at what role FMO3 might play in metabolizing nicotine.
Common FMO3 variant E308G seemed to double the time needed to clear n-oxidation metabolites of nicotine.

This paper :
The research is about nicotine metabolism in humans. In this case they looked at common FMO3 variant E308G and it's effect on nicotine metabolites (the n-oxide part) and also in ability to give up smoking.

Paper :
Nicotine dependence is associated with functional variation in FMO3, an enzyme that metabolizes nicotine in the brain. : click link (abstract)

They say :
FMO3 plays a small role in nicotine metabolism.
But an important role, In n-oxidation.
E308G variant reduced n-oxidation of nicotine by 50% (i.e. double the time to clear the n-oxides).
They say FMO3 (and FMO1) is present in the brain.
They suggest the brain connection may have an affect on how likely a person may give up smoking.

CYP2A6 :
CYP2A6 is one of the group of CYP450 oxidizing (redox) enzymes.
Currently it's regarded a heavy-duty player in metabolizing nicotine metabolites in particular.
FMO3 is also a redox enzyme, but currently regarded a small player.

E308G  variant in FMO3 gene :
E308G is at codon 308 of the 532 amino acid FMO3 protein code.
It's meant to be amino acid E but instead is G (or vice versa. can't recall).
Currently it's regarded 'harmless', but many TMAU people carry it.
About 15-25% of whites are thought to carry E308G.
E308G is the 2nd most common FMO3 coding variant in whites after E158K (maybe 10-40% whites).

In this paper they say E308G may double the time needed to clear n-oxide metabolites of nicotine, and also affect the ability to give up smoking ?

FMO3 in the brain :
CYP2A6 is not present in the brain.
But FMO3 (and FMO1) is.

What's this to do with Systemic Body Odor ? :
My own view is that currently FMO3 is the most likely enzyme at fault in systemic body odor cases.  
This paper in relation to FMO3 :
The paper is really to do with smoking, how nicotine in cigs are metabolized, and any clues as to how enzymes may play a role in stopping smoking. I guess they will look a bit more at FMO3 now. But it may be to try and block FMO3 so the person has a bad reaction to smoking (like antabuse and alcohol).
It should ,lead to more FMO3 research anyway.
The labs listed are spread over USA. Probably a union for research in smoking.

Final thoughts :
Not directly to do with Systemic Body Odor but any research in FMO3 is welcome, as it is a very neglected enzyme due to not being thought important.
It's interesting that FMO is in the brain. May play a role in psychiatric disorders and drug metabolism.
I'm not expecting much from this research (but might be wrong).
FMO3 flaws may mean they are not very good 'smokers'. (?)
E308G is carried by maybe about 15-25% whites, and all of them don't smell, so it doesn't seem that solely carrying E308G results in someone having 'smell problems'. 

FMO3 gene :
532 amino acid code for the FMO3 protein. (exon)
They are talking about the variant at codon 308.
Little known about FMO3, but currently E308G is taught as harmless.

All genes also have a 'junk part' and promoter region etc (introns).
You can have faults in the junk part (introns) that affect the coding. (i.e. perfect 532 code and certain intron faults might still mean sub-par function).


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FMO3 DNA testing
Update Aug 17 :
Genos is back with it's EXOME test
link

Note :
Exome/Genome testing may be better option than single gene testing.

See this post : link

Note : Genos Exome Testing.

Exome testing is almost the same price now as single gene testing. Also Genos is consumer friendly, which standard DNA labs are not.

So the blog offer to test solely for FMO3 is almost obsolete, and so no longer offered.


Does Genos fully sequence FMO3 gene ?

At the moment it is not clear, but hoped this will become clear over the next few months

Note : possible 'wild west' way of testing FMO3
Use an ancestry dna site and rummage through the raw data

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