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

[musicchick581]

musicchick, did you try GABA? Maybe you have a glutamate-toxicity?

I think I tried GABA a few years ago before I knew about this stuff and it gave me more panic attacks. I could be wrong though...I'm going to take an AAE and OAT urine test so it should test that. Hopefully they are accurate.

 

[Gondwanaland]

How about LDN for this case? Does anyone have experience with it?

 

[pemone]

Apparently having the T allele for MAO-A RS6323 means you do not convert catecholamines like epinephrine / adrenalin to metanephrines efficiently. Men have only one half of the allele pair; women have both sides. Does anyone know of a study that quantifies this effect? Specifically what percentage of this conversion gets impaired for people with the T allele?

I'm trying to understand if this is a moderate 5% downregulation, or if it is a very serious 60% downregulation.

I would also like to know what other SNPs would downregulate this same conversion.

I have a problem with high adrenalin and my metanephrines stay always in normal range. So my biochemistry appears to exactly match what these genetics suggest might happen.

 

[thevirusz]

Hi Bluebell,

Interesting to read your comment as I am experiencing exactly the same. I also have MAOA T +/+ and I would consider myself fairly calm and rational. I do however seem to be above average comfortable with stress and can get easily bored. But overall, I simply can't really relate to most of the symptoms described with this.

One of the main reasons to get tested on 23andme was because I feel tired everyday, even though I eat well, sleep enough and exercise. Also, I tend to get sick quite easily. My experience seems to be close to yours which makes it really interesting since we share some very specific genes.

It would be great if anyone with more expertise than me (newbie) could shine their light on this!
Thanks in advance


- Full results below -

COMT V158M rs4680 AG +/-
COMT H62H rs4633 CT +/-
COMT P199P rs769224 GG -/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
MAO A R297R rs6323 T +/+
ACAT1-02 rs3741049 GG -/-
MTHFR C677T rs1801133 GG -/-
MTHFR 03 P39P rs2066470 GG -/-
MTHFR A1298C rs1801131 TT -/-
MTR A2756G rs1805087 AA -/-
MTRR A66G rs1801394 AA -/-
MTRR H595Y not found n/a not genotyped
MTRR K350A rs162036 AA -/-
MTRR R415T not found n/a not genotyped
MTRR A664A rs1802059 GG -/-
BHMT-02 rs567754 CC -/-
BHMT-04 not found n/a not genotyped
BHMT-08 rs651852 CC -/-
AHCY-01 rs819147 CT +/-
AHCY-02 not found n/a not genotyped
AHCY-19 rs819171 CT +/-
CBS C699T rs234706 GG -/-
CBS A360A rs1801181 AG +/-

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.

 

[ahmo]

@thevirusz I share all the above w/ you, different values in 8 out of the 20. I found FMN form of B2 to have a dramatically beneficial effect. I've written about it, last link in my signature.

 

[Oci]

Thanks Everyone for the information. I am still trying to wrap my head around MAOA and MAOB. On my 23andme data there are 24 MAOA snps listed. I have 2 of the same number for 9 or them. What I don't understand is how I find out the risk ones?

On my Genetic Genie results they only list MAO A R297R which for me is GT or +/-

On MTHFR Support they list 8 different MAOA snps and all of mine are +/-. Does this mean they may or may not be a problem? What does +/- likely mean?

Do GG and MTHRF support report the most important ones?

For MAOB, MTHFR support report only lists one and it is -/- . 23andme lists a whole bunch and mine are all homogeneous.

Can anyone help me to understand this?!

 

[alicec]

Do GG and MTHRF support report the most important ones?

GG reports the snps that Yasko is interested in. This doesn't mean they are important, indeed why she singles out a particular snp is often inexplicable.

MTHFR reports a few more that supposedly have some research background to them but you would need to check carefully that the research means anything and that they are interpreting it correctly.

Promethase might be better - at least it ranks the snps based on what is known about them and gives a link to the research.

Unfortunately there is no easy shortcut. Searching on pub med for studies on the snp is your ultimate answer. Sometimes you will find other people who have been diligent and looked at the research. There are some of those threads on PR. You need to be careful whose word you trust however - there are half-baked theories and errors which are endlessly repeated all over the internet.

The subject of this thread is a good example - all sorts of things are claimed for it many of which are contradictory. This particular snp on MAO A is described as R297R. That tells you straight away that it doesn't amount to much since the amino acid arginine (abbreviated as R) at position 297 remains unchanged by the variation in the DNA. The variant and the ancestral gene produce exactly the same protein product.

This snp by itself means nothing.

You will find studies which show this snp might be associated with various conditions (although there is not a lot of consistency as I recall). This could mean that the snp is in linkage disequilibrium with something else that is actually having the effect - ie it is a proxy for something else. I did once start chasing those studies (I am +/- for this snp) but in the end concluded it didn't amount to much.

So what is all this stuff about a low activity and high activity form of the enzyme. The best I can recall about the origin of this notion is the stuff about the so-called warrier gene. There is an area in the promoter of the gene (this is the region just upstream of the part of the gene which codes for the protein; it affects the rate at which the gene is transcribed) which has been shown to be repeated and the number of repeats has been shown to correlate with high or low levels of the enzyme. Not a slow or a fast form but more or less of it.

There is some suggestion that various snps might be proxies for the number of these repeats and so predict whether or not a person produced high or low amounts of the enzyme. rs6323 was one of those, but again not alone, but in combination with others.

Somehow I think this has become garbled into rs6323 produces a low or high activity form of the enzyme.

Again I didn't follow it all up for long but I think there is some discussion about it on 23and me and if you google warrier gene you should find some studies.

Sorry there is no easy answer. In the end I concluded that my several +/- MAO A snps amounted to nothing.

 

[Oci]

GG reports the snps that Yasko is interested in. This doesn't mean they are important, indeed why she singles out a particular snp is often inexplicable.

MTHFR reports a few more that supposedly have some research background to them but you would need to check carefully that the research means anything and that they are interpreting it correctly.

Promethase might be better - at least it ranks the snps based on what is known about them and gives a link to the research.................
.......Sorry there is no easy answer. In the end I concluded that my several +/- MAO A snps amounted to nothing.

Many many thanks Alicec for clarifying this as much as it can be clarified!

I do have some FMN and will try it to see if I feel less anxious on it. I do have an underlying level of anxiety but it is perhaps more connected to my COMT++. And to my present life situation....widowed a year ago and finding my way on my own...plus a couple of deaths in family recently.

I imagine that this info on snps will also apply to some other genes too. I need to find out the significance of each one. So much to research. There are so many different variations and combinations and many more not even tested by 23andme.

It seems to me that other testing ie the ION test I had done some years ago will give a clearer picture of what my body is actually doing/needing. I'd like to repeat that test or do others but they are expensive. Some recommend Nutreval and of course, OAT by Great Plains. I did look at results of one person's that were posted yesterday on http://forums.phoenixrising.me/inde...elp-lots-of-test-results-inside-thanks.39651/

I am not sure how helpful that one would be for me or my doctor who is pretty new to all this. I guess it does identify the dysbiosis and agents that the bugs are sensitive to.

However I have had several stool tests by various companies done over the years and there are few constants except for Candida.

Thanks again!

 

[alicec]

I do have an underlying level of anxiety but it is perhaps more connected to my COMT++. And to my present life situation....widowed a year ago and finding my way on my own...plus a couple of deaths in family recently.

Your present life circumstances would be more than enough to create anxiety. You have my deepest sympathy. I too was widowed, though a long time ago now - almost 20 years. It was certainly a life changing event.

COMT +/+ can certainly have an effect on mental state though the often repeated alleged sensitivity to methyl donors that goes with it is really a myth. It is just someone's supposition and doesn't seem to have much basis in reality.

I've got quite a few COMT +/+ and have read a moderate amount on these snps. Probably no one single snp is especially important but there do seem to be haplogroups of snps that definitely result in a slower enzyme. What that means for an individual is more complex than the proposal that we have too much dopamine. I would love to have more dopamine! It may mean that we end up with a more sensitive negative feedback mechanism. As soon as dopamine starts to rise this kicks in quickly and we end up with low dopamine. That's how it feels with me most of the time anyhow.

A number of COMT snps do seem to be associated with mental illness, usually it is several rather than any single one and often in conjunction with snps on other genes. So there may be some sort of genetic predisposition but it is complex.

I know what you mean about tests - none of them are entirely satisfactory and they are all expensive. I did an ION profile and a Genova GI effects test about a year ago and was fairly underwhelmed with what I learned in comparison with the costs. The ION profile has cut back on some of the test parameters now that Genova alone is in control and while I was interested in the stool test since I hadn't had one for some time, I couldn't see the point of having another one.

Since doing a uBiome test I really wonder what if anything the culture based part of stool tests means. The organisms identified seem to have no relationship to those identified by DNA sequencing.

I've fallen back to having a GPL OAT a couple of times a year. It lets me keep an eye on oxalates plus some nutritional, metabolic and microbial markers and is not too expensive but I agree with the point made by @JaimeS on the other thread you referenced. I can find no reference for arabinose being a marker for Candida. D-arabinitol as used by Genova yes but not arabinose. GPL have special claims to this marker so maybe they have research they are not telling anyone about.

 

[Oci]

Many thanks once again, Alicec. It is good to know that others find widowhood a life-changing event. I'm finding the second year harder than the first in some ways. It is the realization that I am on my own now and may be for a very long time. I was married for 47 years and together with my husband for 5 years before that. Now I am working on finding out who I am as a single.
Also tackling some big decisions such as how much money will I need for the rest of my life, where would a more economical place to live be.

I do remember you telling me before about the effect of methyl donors on COMT++. I believe you. My eldest daughter was highly sensitive to even small amounts of MB12 but her practitioner had her very slowly work up to a regular amount. I'm sure given her personality that she is COMT++. I was blaming COMT++ for a foggy head there for awhile and the taking of methylated vitamins but then figured out another cause ie candida (foggy head disappeared when I took a course of Diflucan.)

I have not added back MB12 or folate yet. I've been taking Yasko's All-in-One for 2-3 months and not adding any extra B12 or folate. I'm planning to test and find out if I actually need them first. I'm not sure which test yet. Would OAT show this? On my past ION test I did not need B12. Not sure re folate. I try to eat my leafy greens. I'd like to have a baseline first before adding too much. I already take an awful mess of supps. Its a bit ridiculous and I want to reduce.

You said...
"I've got quite a few COMT +/+ and have read a moderate amount on these snps. Probably no one single snp is especially important but there do seem to be haplogroups of snps that definitely result in a slower enzyme. What that means for an individual is more complex than the proposal that we have too much dopamine. I would love to have more dopamine! It may mean that we end up with a more sensitive negative feedback mechanism. As soon as dopamine starts to rise this kicks in quickly and we end up with low dopamine. That's how it feels with me most of the time anyhow."

I also have VDR Taq++. I've forgotten how that plays in.

I am interested in knowing about haplogroups of COMT snps. I too would love to have more dopamine! I have read that diet coke raises dopamine. I find it really gives me a boost. It is both the caffeine and the aspartame, I believe. However, I mostly avoid having it these days as there is so much written about it destroying the brain.

You said..."I know what you mean about tests - none of them are entirely satisfactory and they are all expensive. I did an ION profile and a Genova GI effects test about a year ago and was fairly underwhelmed with what I learned in comparison with the costs. The ION profile has cut back on some of the test parameters now that Genova alone is in control and while I was interested in the stool test since I hadn't had one for some time, I couldn't see the point of having another one."

Thanks for the comments about the various tests. Good point about changes made by Genova. I had the Metametrix GDfx a couple of years ago and it told me nothing. Said 4+ yeast but could not culture and said transient.

You said..."Since doing a uBiome test I really wonder what if anything the culture based part of stool tests means. The organisms identified seem to have no relationship to those identified by DNA sequencing."

My last stool test done in June was by Doctor's Data and it identified candida 2+ and a couple of bad bacteria. Maybe of value re showing slightly low butyrate and low SIgA. Something to work on.I have not done Ubiome yet.

You also said..."I've fallen back to having a GPL OAT a couple of times a year. It lets me keep an eye on oxalates plus some nutritional, metabolic and microbial markers and is not too expensive but I agree with the point made by @JaimeS on the other thread you referenced. I can find no reference for arabinose being a marker for Candida. D-arabinitol as used by Genova yes but not arabinose. GPL have special claims to this marker so maybe they have research they are not telling anyone about.

Interesting...I will keep in mind. Thanks again.

PS: I can't figure out how to integrate snippets of previous post into my reply. I would really appreciate help on this!

 

[alicec]

I also have VDR Taq++. I've forgotten how that plays in.

That is one of the inexplicable snps which Yasko was interested in. It doesn't seem to do much.

In her admirable attempt to educate us about snps @Valentijn started a thread on VDR snps here and one on COMT here.

Ive made myself a large table where I record my research on snps but often find as the brain fog sets in I forget to record where the research came from so I can't always find the reference!

In my notes on COMT I say
rs4680 (AA +/+) a well characterised snp which does change the protein structure resulting in a slower enzyme;
snp alone very modest assoc schizophrenia, psychosis, Alzheimer’s, worse in combination with other snps which I don’t have; this is worrier snp, giving advantage in memory and attention to tasks; more vulnerable to stress; snp alone shows more sensitivity to pain but less need for morphine as well as being part of haplogroup defining pain sensitivity; assoc CFS/fibromyalgia

rs6269 (AA +/+) non-coding; snp assoc with CFS/fibromyalgia; more sensitive to pain (23andme)

rs4633 (TT +/+) coding but no change to protein

The above two snps, in combination with other non-coding snps may exert an effect through changes to secondary mRNA structure which in turn affects translation into protein.

The above three snps, plus implied rs4818 (not measured by 23andme but in close LD with rs4680) form a haploblock with significant influence on pain sensitivity – I have intermediate pain sensitivity (higher than normal but not highest)

I don't have the haploblock 2 combination (as described in PR thread) so thankfully don't have the very slow enzyme combination.

Here are just a couple of references to give an idea of the complexity of COMT alone or in combination with other genes.

I read quite a bit of stuff but in the end concluded I didn't have some of the potentially really bad COMT combinations and I wasn't going to worry too much about it, though is an issue for me to at least some extent.

 

[Oci]

Thanks so much! I have rs4680++ and rs4633++ but not the middle one. I also have rs174675++ and rs74060++. The more I learn the more I realize how complicated it all is. And there are many many more snps that are not tested. I'm just looking at the MTHFR list. I find it all very interesting but like you, am not going to worry about COMT too much.

What I am worried about is the Alzheimer genes or snps. I really prefer to not know! I was reluctant to do the 23andme test until I realized that I could opt out of knowing about Alzheimers and the other serious diseases. I know I could look it up in the raw data but won't. I have not run my data through Prometheus for fear of learning about susceptibility to Alzheimers. Besides I am already overwhelmed with information.

I guess this concern is because one of my grandfathers had early onset Alz and one aunt had some dementia. A freind's husband has early onset too. And aren't we all concerned about Alzheimers. I do know about my cancer risks as there has been so much of it in my family. I just don't want to add concern re Alzheimers. As far as any of these diseases is concerned, I think our best bet is to look after ourselves the best we can and enjoy life to the fullest - live in the present.

 

[Oci]

@alicec and anyone"

Alicec said: "Since doing a uBiome test I really wonder what if anything the culture based part of stool tests means. The organisms identified seem to have no relationship to those identified by DNA sequencing."

I am thinking of ordering a Ubiome test - their 5 for 1 offer - but wonder in what way it might help me? Offer end tonight. Or should I save my money for the OAT test?

 

[alicec]

I am thinking of ordering a Ubiome test - their 5 for 1 offer - but wonder in what way it might help me? Offer end tonight. Or should I save my money for the OAT test?

This test will look at your microbiome in 5 different body sites. Interesting no doubt but you will then need to spend energy on understanding what each of the different sites mean. Maybe it would be better to just get a gut test - usually I think USD 99. Sometimes they have specials on the gut test alone.

 

[Oci]

This test will look at your microbiome in 5 different body sites. Interesting no doubt but you will then need to spend energy on understanding what each of the different sites mean. Maybe it would be better to just get a gut test - usually I think USD 99. Sometimes they have specials on the gut test alone.

Thanks Alice. I think you're right – it would be a major project to figure it out… If I even could.

 

[thevirusz]

@thevirusz I share all the above w/ you, different values in 8 out of the 20. I found FMN form of B2 to have a dramatically beneficial effect. I've written about it, last link in my signature.

Thank you for the tip. Is just started last week at about 7000% RDI of vitamine B2.
How long was until you noticed any effects?

Has anyone else recognized themselves in my previous description?
And have you undertaken other succesful dietary changes to influence this (tired, slight depressive tendancy, poor immunesystem)

Thanks in advance for all the feedback