More Evidence Net Deficiency Is Associated With Pots

[jangle]

http://dmm.biologists.org/content/early/2013/04/03/dmm.012203.abstract

They found that mice deficient in NET proteins was sufficient to produce the postural tachycardia with many of the associated symptoms.

In the majority of our cases, I don't think it's due to a genetic defect, but rather the epigenetic "switching off" of the expression of the gene - likely due to inflammatory factors. As found by Bayle's group.

[Zap]

This is interesting - and it would be even more so if we could cross-reference with our data to verify a lack of a genetic defect. That would pretty much prove your idea that this is more epigenetic in nature.

In that light, maybe that is why anti-inflammatory drugs (steroids) prove helpful for some, which begs the question: Is the NET dysfunction for some/many of us secondary to some type of unknown autoimmune/inflammatory disorder or process?

[jangle]

This is interesting - and it would be even more so if we could cross-reference with our data to verify a lack of a genetic defect. That would pretty much prove your idea that this is more epigenetic in nature.

In that light, maybe that is why anti-inflammatory drugs (steroids) prove helpful for some, which begs the question: Is the NET dysfunction for some/many of us secondary to some type of unknown autoimmune/inflammatory disorder or process?

Probably, but unfortunately the (clinical) research process is cold, rigid, and slow.

I am however excited that vanderbilt is behind this study, as before there really wasn't any major academic US institution pursuing NET - it's currently mostly being done in Australia.

Again, facing the options of treatment for such an autoimmune illness. It would probably be IVIG, as IVIG is the most reasonable treatment in an unreasonable environment.

Ideally, we'd be able to identify the specific autoantibody or cytokine, develop a specific drug that targets such thing, and utilize that.

[issie]

I bumped up a discussion from a while back on this when Dana was researching SLC6A2 in relationship to our 23&me data - trying to sort out our mutations.

If you do a search on Google there are articles and research going back into the early 2000's where they have connected this to POTS and felt that this played a role in the illness.

Like Jangle said, most of the research I found was out of Australia. And as Zap said the thought was epigenetic changes causing it. So, hope they keep researching it and figure it out for us. I found one article connecting the snp to be rs5564. We have this on our 23&me testing.

Issie

[Birdlady]

Hmm. I think Vanderbilt needs to move away from this single mutation and run with a larger theory that would include more of us like an epigenetic concept. Only 1 or 2 families in the world have this mutation, so I don't really understand why they keep beating a dead horse. We already know about this one. Does anyone else feel that way?

There are 16 missenses on the NET gene. The lead researcher on this paper has done a few for ADHD in the past, which did show some disruption in transport. But for whatever reason they are SOO focused on the A457P mutation. It's useless and nothing new...

[issie]

Dana,

Did you ever figure out if that snp that you found on your NET gene was an issue or not? Or did you stop looing into it?

Issie

[Birdlady]

My doctor was not interested (out of his league more like it) and I never heard back from Vanderbilt on it at all. I kind of just gave up after that... lol The lead on this paper Maureen is who I emailed.

[issie]

Too bad, because I think you were on to something. So many of us have thought that NET is a player and getting the problem figured out may give us more answers. I hope they start to look at the whole picture and not just the one part of it. Cause, like you say ---there has to be a bigger picture to this. They just need to look into it more.

Issie

[ramakentesh]

I think the evidence of wider epigenetic suppression of net was reviewed with interest by Vanderbilt and others.

[ramakentesh]

Purely out of interest - there are some herbs that are reputed to increase the function of remaining net if some are present and in terms of epigenetic gene suppression foods that contain or are reputed to contain histone deacetylase modifying activity - in broccoli, tumeric and onions in particular.

[issie]

I think the evidence of wider epigenetic suppression of net was reviewed with interest by Vanderbilt and others.

Yeah, but have they continued to try to find the complete answer with it? We have so many leads --even from just our own personal experience and what we feel is going on. Looks like we could get it all together in one place and present what we have discovered about ourselves --with lots of trial, error and research and maybe something get further looked into and something done about it. (Ohhhh, feel a rant coming.)

Turmeric and ginger are my friends! Help in so many ways.

Issie

[Angela]

Purely out of interest - there are some herbs that are reputed to increase the function of remaining net if some are present and in terms of epigenetic gene suppression foods that contain or are reputed to contain histone deacetylase modifying activity - in broccoli, tumeric and onions in particular.

so we are running out of net? i bet the fish will be happy.

[ramakentesh]

I think the evidence of wider epigenetic suppression of net was reviewed with interest by Vanderbilt and others.

Yeah, but have they continued to try to find the complete answer with it? We have so many leads --even from just our own personal experience and what we feel is going on. Looks like we could get it all together in one place and present what we have discovered about ourselves --with lots of trial, error and research and maybe something get further looked into and something done about it. (Ohhhh, feel a rant coming.)

Turmeric and ginger are my friends! Help in so many ways.

Issie

Im not really sure what you mean. Epigenetics and mutations are very different. the complexities of epigenetic gene expression and suppression are highly complex and poorly understood even by the experts.

[issie]

Lots of research going on about it with those in the genetics field. Lots of connections they are finding with genetics and illness. They are actually figuring out what genetic markers are associated with certain illnesses, malfunctions in the body, hair color likeliness, eye color etc ---just with gene testing. If all this can be determined with a saliva or blood test and compared with others on the level that this is taking place. Why couldn't they take all of us Potsies and genetically test us and find the relationship, similarities and find out if this is a genetic mutation or a genetic epigenetic thing? I'm sure we'd all be willing to give some saliva or blood to find out.

With epigenetics if that is what has happened - what triggered the change and what could be done to prevent it. If it's genetic and we've inherited a certain gene - is there some way to avoid it turning on and it being an issue. Just because one is a carrier - doesn't mean there will be a problem. But, when something becomes a problem --what made that happen. Do we just say we are born that way and give up and stop trying to find answers? I don't think so. (Some of us think that maybe a vaccine triggered something to cause us to have dysautonomia. More research needs to go into what maybe is the trigger and then maybe others won't in the future either be exposed to the trigger or they will find a way around it.)

With some of the research on the genes and the pathways of function. Some are finding mutations on these genes and assumed malfunctions in certain pathways of function. It is very new and really in it's infancy of discovery. But, with what is thought to be known about this ---some are using certain supplements to make these pathways work better. Supporting the bodies detox pathways and assimilation of nutrients when there is a fault there. Many are saying that they are getting really good results from this. (I'm learning about this and don't really know enough about it to talk about it with any intelligence. There are others that know way more then me.) But, I find this very interesting and think it may have some weight to it. I think it will evolve with time and will be tweaked along the way. But, the amount of change that some are having can't be denied. The little bit that I've figured out with my mutations and making the diet and supplement change has made a difference.

I subscribe to Scientific American magazine and this months magazine has an article in it about stem cells and them starting to be able to cause cells to regenerate. They know the liver can regenerate - even with a small amount left in the body. They are thinking they can cause this to happen with other organs in the body. Like for example if a lizard loses it's tail - it can regrow a tail. What happens to allow this and why does the liver do this and no other organ can? There is a lot of science that is not yet known. But, if one can think up something ---eventually it can be done.

I just wish they'd come up with a way of comparing our genes and seeing if there is a common mutation or epigenetic change somewhere that predisposes us to having the issues. If they could find a connection there might be something that could be done about it. For example --we are all born with the inherited predisposition to get or have cancer. Why do some get it and others don't. Same with POTS ---what is it that causes some of us to get it and others don't. And when there is a family type connection with dysautonomia --like in my family. Why is it there and what is it in the gene pool that has caused this to be a family thing ---yet present in different ways. I have POTS and my sis has OI and two of her kids have POTS --the doctors think-- and my grandmother had POTS, we think. Is it an organism that was passed in birth to us that was a pre-birth type epigenetic thing or is an inherited mutation on a gene? Is it a faulty immune system that maybe can be figured out and something done about? There is so much that needs to be looked at with POTS that doesn't appear to be looked into yet. If I can sit here and think of these things --someone much more intelligent then me can think of these things and maybe have the knowledge, resources, money and backing to try to find the answers.

Rama, I think you just wanted me to go on my rant. I think you got me too. LOL! Oh well ---I do wonder these things.

Issie

[ramakentesh]

Normally but not always epigenetic modifications of gene expression are acquired during a person's life although in limited circumstances some can be heritable. But the gene looks normal and is normal. It has just been silenced by extragenetic means.

As for examining the genes themselves of POTs patients - its been happening since at least 1998. No common genetic marker has been identified in POTS patients other than the defect in ace2 in a small subset. There are many papers on genetic markers in POTS.

[issie]

I was accepted as a test subject for MPN due to my having mast cell issues. This study is being done by 23&me. They take known people with known problems and lump us together and test hundreds of thousands of genes and find the connections. Why couldn't something like this be done with dysautonomia. Maybe get us into the subsets that we "think" we are in and compare notes. My DNA is on file indefinitely and when a new test is available (for anything related to genes) they test me for it. I get the results of my snp's and the correlation to it and the illness that they are testing for. Why can't we have something like this looked into. How many of us are there? How many of us would jump on this as a thing to do? ALL OF US!!!!

Issie

[Angela]

waiting for my results.

[Angela]

last test inflammatory factors

[Angela]

http://www.ncbi.nlm.nih.gov/pubmed/21983856

[issie]

Good find Angela! Did you get tested for this?

Issie

[Angela]

Gaba? no

[issie]

No GAD65? Test antibodies.

I can't use GABA the amino - has a paradox reaction with me. Instead of calming me down - keys me up. I had someone explain this to me one time - something about how things are metabolized. But, don't remember exactly what was said. I think if we could get GABA to work on our parasympathetic system it might calm the hyper surge affect down. Not sure how to do this though. Someone I was recently talking to - said the best way is with diet. Avoiding glutamates. Which I do already.

Issie

[DoozlyGirl]

Here are several publications that I have found. Hope none of them are duplicates what was already shared in this thread.

http://www.nejm.org/doi/full/10.1056/NEJM200002243420803

http://www.ncbi.nlm.nih.gov/pubmed/12438171.

http://www.ncbi.nlm.nih.gov/pubmed/11458707

http://www.ncbi.nlm.nih.gov/pubmed/12589229

Lyn

[issie]

A little info on glutamate - where found: Connections to vaccines, foods, dairy, protein etc.

http://www.truthinlabeling.org/hiddensources.html

Issie

[ramakentesh]

NET defiency even seems to cause hyporeninism.

NET low in many POTS patients:

http://www.ncbi.nlm.nih.gov/pubmed/19808400

NET reduced perhaps because of epigenetic (acquired) mechanism:

http://www.ncbi.nlm.nih.gov/pubmed/22723437

Reduced MIBG uptake in cardiac muscle - suggestive of cardiac denervation or NET deficiency:

http://www.ncbi.nlm.nih.gov/pubmed/19687022