Rs6323 - MAO-A - What this gene does if its bust

[snowathlete]

I looked at my 23andme dna data and picked out those that also appear on the Yasko panel, which as i understand it, is mainly (entirely?) about the methylation cycle.
This post helped me do it, but I didnt want to hijack that thread, so I started this one instead.

The outcome of this little exercise is that these are my three most dodgy genes:
Rs6323 - MAO-A R297R +/+ (T)
MTRR A66G +/+ (GG)
MTRR-11 A664A +/+ (AA)

Im going to try and look at each in turn, starting with Rs6323 - MAO-A R297R +/+ (T) in this thread.

This is the wikipedia article on MAO-A:
http://en.wikipedia.org/wiki/Monoamine_oxidase_A

It talks about Brunner syndrome. Is that relevant?

It also talks about inhibitors at the bottom, but I dont yet understand, does a T mean that I have LOW or HIGH levels of the related MAO-A enzyme?

Looking at the heartfixer site, it seems to be saying that the enzyme that this gene expresses is supposed to turn Serotonin into HIAA - which I think is this stuff:
http://en.wikipedia.org/wiki/5-Hydroxyindoleacetic_acid

And it says that you pee this stuff out - so presumably that means this is how your body gets rid of serotonin when its done with it. In turn that seems to suggest that too much MAO-A and you break down too much serotonin, and too little MAO-A and you end up with too much.

Well, I welcome anyones thoughts or knowledge on this.

 

[globalpilot]

Hi,
I also have the same result as you for this gene both through Yasko and 23andme. However, if you look at this it is saying that T is the ancestral allele which I imagine is the normal and G is the minor.

So, I think the T may be the normal allele.

Can anyone confirm this ?

http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs6323

GP

 

[snowathlete]

From what I read there is a lot of debate and disagreement on what is normal on many genes as in a lot of cases the split is close to 50% across the population. I've based my status on what yasko seems to say about these genes.

 

[nanonug]

Im going to try and look at each in turn, starting with Rs6323 - MAO-A R297R +/+ (T) in this thread.

There is a big threat on 23andme about this SNP. Honestly, I don't think it amounts to much, just by itself at least. I have no idea why Yasko has it isolated from other MAOA SNP's.

 

[snowathlete]

nanonug - thanks for posting that link. Its very interesting.

I think they are saying that T is the low activity variant, but they seem to be in doubt as to whether or not that one bit determines the whole gene or not.

They mention a couple of other values and the one of the two I have points to MAO-A being low activity and the other high. So, 2/3 low, from the limited info i have available
rs2072743= T (C) = High activity MAO-A
rs1137070= C (T) = Low activity MAO-A
rs6323=T (C) = Low activity MAO-A

Im left, thinking, well, Yasko seems to know what she is doing and is very well qualified etc, so I myself am leaning toward this meaning that the MAO-A is low activity for me.

Yasko has a product to treat this, has anyone tried it?

 

[nanonug]

from the limited info i have available
rs2072743= T (C) = High activity MAO-A
rs1137070= C (T) = Low activity MAO-A
rs6323=T (C) = Low activity MAO-A

Huh, could you clarify the T(C) and C(T) thing? I'm not sure I understand...

Im left, thinking, well, Yasko seems to know what she is doing and is very well qualified

Hmm, I have a much harder time trusting as I am skeptical by nature.

 

[determined]

I'd also like to know if Yasko's information is based on observations or some type of published information. Thanks!

 

[snowathlete]

A/t and c/g are the same thing effectively but different groups quote one or the other. It depends which side of the chromosome you are looking from.
23andme tend to quote one and most science papers quote the other. Don't know why.

There is another thread somewhere about yaskos credentials and her papers. I figure that to get through this I have to trust somebody along the way.

 

[Pea]

Snow, is your serotonin or dopamine low, or high, or is that your question?

I know about low serotonin.

 

[nanonug]

A/t and c/g are the same thing

What I am asking is why you have, for example, a "T" followed by a "C" in parenthesis. Basically, I don't understand what that means.

 

[snowathlete]

What I am asking is why you have, for example, a "T" followed by a "C" in parenthesis. Basically, I don't understand what that means.

ah its an error, I meant:

rs2072743= T (A) = High activity MAO-A
rs1137070= C (G) = Low activity MAO-A
rs6323=T (A) = Low activity MAO-A

Pea, i havent tested my serotonin yet, but do plan to.

 

[greenshots]

I agree, those MTR/MTRR defects are a huge issue. You may want to read up on Dr. Richard Deth's work in these enzymes, he's the guru here. I'd also highly recommend you read Dr. Vank's Sweden lecture when he discusses these.

The MAO-A spares serotonin. Trouble is, like any thing else, hormones are based on a feedback system and so once levels get high with the MAO A, it sends the message to shut down serotonin production and then your super low. People with this defect are known to be more emotionally up & down and have anxiety, insomnia, depression, OCD, eating disorders, etc. Its doesn't mean you'd have every issue just usually a couple. The angriest most volatile autistics have the double MA0-A so score 1 for not being autistic!

Anytime you eat any foods high in tryptophan, the body's serotonin precursor, you'll cause fluctuations too. I've always wondered if this is why they say "going bananas" since they are high in tryptophan and autistic kids usually LOVE them and then they go bananas.

Just some pondering....
Angela

I looked at my 23andme dna data and picked out those that also appear on the Yasko panel, which as i understand it, is mainly (entirely?) about the methylation cycle.
This post helped me do it, but I didnt want to hijack that thread, so I started this one instead.

The outcome of this little exercise is that these are my three most dodgy genes:
Rs6323 - MAO-A R297R +/+ (T)
MTRR A66G +/+ (GG)
MTRR-11 A664A +/+ (AA)

Im going to try and look at each in turn, starting with Rs6323 - MAO-A R297R +/+ (T) in this thread.

This is the wikipedia article on MAO-A:
http://en.wikipedia.org/wiki/Monoamine_oxidase_A

It talks about Brunner syndrome. Is that relevant?

It also talks about inhibitors at the bottom, but I dont yet understand, does a T mean that I have LOW or HIGH levels of the related MAO-A enzyme?

Looking at the heartfixer site, it seems to be saying that the enzyme that this gene expresses is supposed to turn Serotonin into HIAA - which I think is this stuff:
http://en.wikipedia.org/wiki/5-Hydroxyindoleacetic_acid

And it says that you pee this stuff out - so presumably that means this is how your body gets rid of serotonin when its done with it. In turn that seems to suggest that too much MAO-A and you break down too much serotonin, and too little MAO-A and you end up with too much.

Well, I welcome anyones thoughts or knowledge on this.

 

[Sparrow]

I am MAO A ++, tested via Yasko, and agree with what Angela had to say. It means you break down serotonin much more slowly than most people. ...But that also means that your levels can sometimes get too high temporarily and then too low in compensation.

My serotonin shows up a bit low on tests, but this dysfunction means that I have to be VERY careful about any efforts to try to increase it. In particular, any interventions need to be very low dose, and spread out over the day (because too much at one time will spike me and cause my mood to plummet). I haven' t experimented with little bits over the course of the day as Yasko suggests because by the time I got her results I had already balanced out my mood issues. I know that 5-htp and other serotonin boosters taken once per day made me really moody (which makes sense based on Yasko's analysys). And my doctor's attempts at prescription antidepressants were a disaster.

This mutation seems to be part of what makes me naturally prone to mood swings - I can be perfectly happy one moment and then weepy the next (I've heard it can also cause aggression, though that doesn't seem to be a big issue for me). I've pretty much eliminated that now through the supplements, etc. I take, but I know that my base state is much more moody than others. It also probably explains why I'm generally a very content type of person, though, so it's not really a bad thing overall. And with my other mutations lowering my BH4 levels, this one may be part of what's keeping me from getting depressed.

In general, tiny tiny doses of most mood-affecting supplements, and spread out several times a day rather than all at once.

The biggest differences in regulating my mood, personally, came from stable blood sugar (that's my other issue, though, not necessarily related to this one. I was just made to be moody, apparently :Retro smile, Douglas Labs "Brain Calm" 2x/day, and dark chocolate in numerous small doses throughout the day. That last one seems to apparently be really critical for balancing me out, but I think that's probably rare in the overall population. Can certainly tell when I've gone too long without my chocolate, though.

For what it's worth, Yasko's observations based on my genetics have all lined up very, very closely with tendencies I was already noticing. I wasn't sure how much to trust her at first, but I think she's on to something. Not sure she actually knows how to truly cure things yet, but I give credit to her explanations of the reasons behind them.

 

[Star-Anise]

Hi all, I am appreciating this thread! Thanks so much for sharing your info
Sparrow
greenshots
I found your information useful in particular, thanks. I just want to make sure I have this right:
I have MAO A R297R (rs6323) ++
I definitely identify with mood fluctuations! And until recently seemed to be stable on a Tryptophan/5-HTP/Melatonin dose at night to help sleep. When I started methylation supports and CBS protocol however, I had to wean myself off the Tyrosine support I was on as well as now, it seems, I'm feeling better as well with weaning myself of the serotonin support too!
My hunch is that I freed up some BH4 that is helping me regulate and use my neurotransmitters that I'm producing naturally.
From Wikipedia:

Monoamine oxidase A is an enzyme that degrades amine neurotransmitters, such as dopamine, norepinephrine, and serotonin.

So if I have the double mutation, then this means that this enzyme may not be functioning optimally with me, and I am not always degrading serotonin, or other neurotransmitters effectively, and this can lead to pooling and then a downregulation in production as a result = mood swings?
I think this is what Greenshots said:

The MAO-A spares serotonin. Trouble is, like any thing else, hormones are based on a feedback system and so once levels get high with the MAO A, it sends the message to shut down serotonin production and then your super low. People with this defect are known to be more emotionally up & down and have anxiety, insomnia, depression, OCD, eating disorders, etc. Its doesn't mean you'd have every issue just usually a couple. The angriest most volatile autistics have the double MA0-A so score 1 for not being autistic!

Anytime you eat any foods high in tryptophan, the body's serotonin precursor, you'll cause fluctuations too. I've always wondered if this is why they say "going bananas" since they are high in tryptophan and autistic kids usually LOVE them and then they go bananas.

My question is then is serotonin support generally to be avoided or as Sparrow suggested, only slow throughout the day if needed at all?
WOW! no wonder i've been having issues. It's just remarkable that before I started methylation and ammonia support my body acted like it reeeeaaaaalllly needed that Tryptophan/5-HTP/Melatonin combo for yeeeeaaarrrrs....!
I crave Bananas like crazy! This is so fascinating. I was thinking the craving for bananas arose out of my need for potassium, but perhaps not! I do see that I get moody sometimes afterwards.... thank-you so much for your input. I love this forum! Star

 

[greenshots]

That's a good question Star-Anise but there's also been debate about whether MAO might act as more of an upregulation like CBS instead of a downregulation like COMT so that these people lose more and need more serotonin for that reason. IDK for sure but it does seem like anyone with that defect needs more, not less. I think your probably right about freeing up Bh4 to make them on your own

 

[Bekah]

Hi all,
Have been reading on here for months regarding the gene angle of health - you guys here really rock with your advice!

I just wanted to join so i could share with what i'm discovering too.
I'm looking into the MAO gene, and it looks like the MAOA rs6323 G/T result is an upregulation of activity:

http://en.wikipedia.org/wiki/Monoamine_oxidase_A
"In patients with major depressive disorder, those with MAOA G/T polymorphisms (rs6323) coding for the highest-activity form of the enzyme have a significantly lower magnitude of placebo response than those with other genotypes.[15]

So we are to presume by this that MAOA is breaking down dopamine, serotonin and norepineprine faster than normal with this snp? Like you said angela, similar to the CBS upregulation.

I have the G/T version of this snp for MAO and do have adrenalin issues coupled with regulating mood issues. I have a few genes mutated when it comes to the neurotransmitters! Have been trying to figure out if too low or too high neurotransmitters are my problem before starting a protocol.

Anyone on here with this snp tried 5-HT or L-dopa and found improvements?

 

[juniemarie]

I have this SNP but the T/T version +/+ which I think is the slower version. The only thing I can add is that I have read that it does not hang on to it's co factors very well and it needs B2 and R5P to work......small doses throughout the day. I also read that you need to be careful about taking mag glycinate and 5-htp

 

[Star-Anise]

juniemarie
Hi there, thanks for your comments re: B2, I was thinking of introducing this for another reason, and you have given me more reason!
re: mag glycinate, can you comment as to what you have found re: cautionary advice for MAO A mutations?

Yes 5-HTP has been a bit of a double-edged sword for me as well. For a long time it seemed that my body needed it, but like my friends on SSRIs, supplementation of 5-HTP and Tryptophan only seemed to improve my mood to a point, and then I stopped noticing improvements.

I have found more success in working on eliminating those factors that may cause my MAO A gene to become unstable, i.e. aluminum detox as Yasko suggests, and removal of sulphur to support BH4

Bekah
I have been thinking of trying mucuna pruriens to support dopamine production as it contains high amounts of L-Dopa. I will let you know if it helps. I'm COMT-/-, and have had success with supporting dopamine production with Tyrosine, and Phenylalanine before, but had to wean off these when I did my sulphur detox. As my mood seems to still fluctuate and I have issues with motivation, I was thinking that perhaps I still need support for dopamine. Unsure about this one.

So we are to presume by this that MAOA is breaking down dopamine, serotonin and norepineprine faster than normal with this snp? Like you said angela, similar to the CBS upregulation.

Yes this is my understanding, however, as Yasko says, it can also cause fluctuations causing too much serotonin, or pooling as greenshots and I were discussing above. This has definitely been my experience. And this is what I'm observing with my husband as well who has MAO A +/+ as well.
Star

 

[Valentijn]

"In patients with major depressive disorder, those with MAOA G/T polymorphisms (rs6323) coding for the highest-activity form of the enzyme have a significantly lower magnitude of placebo response than those with other genotypes.[15]

There's a bit of confusion going here, which is pretty understandable Your version of that MAOA SNP (GT) is your genotype. But that quoted line isn't listing which genotype is problematic, it's just saying that some version of MAOA rs6323, which has G or T as allele options, has that effect.

You need to read the study to see which version (polymorphism) is most relevant. The heterozygous genotype is usually milder than a homozygous polymorphism - if a study finds that the heterozygous genotype is the riskiest, it's usually a good sign that the study's sample size was way too small

That study isn't available to read for free, but the answer is in the abstract: "Subjects with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme (G or G/G). . . ." So GG is the relavent genotype for having the faster version (or G for males, since MAOA is on the X chromosome).

 

[Bluebell]

The MAO-A spares serotonin. Trouble is, like any thing else, hormones are based on a feedback system and so once levels get high with the MAO A, it sends the message to shut down serotonin production and then your super low.
People with this defect are known to be more emotionally up & down and have anxiety, insomnia, depression, OCD, eating disorders, etc. Its doesn't mean you'd have every issue just usually a couple.
The angriest most volatile autistics have the double MA0-A so score 1 for not being autistic!

If this is talking about the majority allele, TT, which Dr. Yasko calls the risky one, +/+, that is what I have --TT--, but I really am not emotionally up and down at all. I am calm and collected almost all the time. I am steady, thoughtful, strategic, good in a crisis. When I get angry it's such a foreign experience that I'm terrible at it. I don't have insomnia, anxiety, eating disorders.

I do have a type of depression but it doesn't really vary, it's kind of a constant anomie that in some ways I've had since I was a child, but I'm not doom&gloom or self-critical, etc. It is certainly influenced negatively by my lack of energy, lack of health, and lack of motivation, but I think these lacks cause a feeling of depression, and not that the existence of depression is causing the lack of energy, health, and/or motivation - if that makes any sense.

There must be other factors going on with the way I'm wired, because my temperament is mostly the opposite of what this MAO-A mutation apparently predicts.

Are there companion mutations that might coexist with the MAO-A's slow breakdown to make the larger neurotransmitter system work in a steady fashion, instead of these big highs and lows that other people apparently experience with +/+ MAO-A?

I'm afraid I don't understand the larger biochemical context of what it means to have a slower breakdown of neurotransmitters, so I am at the limit of my understanding when just talking about these associated behaviors/characteristics.

====
Does any of this have anything to do with how taking 1 measly capsule of sunflower lecithin (1200 mg) sent me on a 5-hour all-night-long sleepless relentless "hot flash" and then absolutely wiped me out for the subsequent 24 hours? Is that due to adrenalin or something? Is this where my +/+ MAO-A has some sort of bottleneck?

[I took it 3 days - first time it just made me feel warm for a while, maybe 30 mins. Second day it gave me a 2 hour really warm, waking up in the middle of the night type of thing, but it cleared and I could go back to sleep -- and I'm cold-natured so it's not in my experience to have hot flashes. Third day it picked me up and threw me around like King Kong, as mentioned in the above paragraph.]

Or what in the heck was going on there? I thought that lecithin was a benign part of Rich's protocol, before the heavyweights of B12 and B9 come into the frame.

====
One thing I think is interesting is why any version of this allele would result in less of a placebo response (which is mentioned in the Wikipedia reference above). What is it about the other versions of this allele that would allow more of a placebo response? (not really due to a drug action, but due to a kind of imaginary expectation that it would work)