The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Anyone here with homozygeous GAD1 genes?

Discussion in 'Genetic Testing and SNPs' started by Azrael, May 21, 2014.

  1. Azrael

    Azrael

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    Hi

    I found out just recently that i have 2 homozygeous GAD1 genes as well.

    Im just not sure what sort of impact it does cause there are more green GAD1 genes than red according to my report.

    Is there certain GAD1 creating more implications than others?
     
  2. Where did you get your report done. I ran my 23andMe through GG and Promethease but Never saw GAD on the lis (or NOS), so I am curious!
     
  3. Azrael

    Azrael

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    Hi Squid

    I did Prom and one other not sure if it was GG. But to be honest I didnt want to skip some other important SNp's so I went for sterlings app over at mthfrsupport. It will cost you $20 though. I wish I did that first though, just because you miss out on a few by not doing so.

    Sterlings App

    Here is another link at the bottom where a guy (Eric) tells about his own gene problems - and his own SNP examples on frontpage is taken directly from his sterling app report.

    I would say this, im glad i picked sterlings app cause I didnt have the full picture before.

    On this page from Erics website (his own genetics) you can read about all the other SNP's you get from sterlings app.
     
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  4. Thanks! This is fantastic. I'll see what I can find out for you about GAD too if I come across it.
     
  5. Azrael

    Azrael

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    Good luck to you Squid.

    I have searched a bit for it too, but just found out some basic knowledge about it.

    The GAD genes are responsible for conversion from glutamic acid/glutamate to GABA the wonderful calming neurotransmitter.

    So if one have mutations it would results in less GABA from Glutamate, therefor a buildup of Glutamate is a possibility.

    Glutamate is an excitory instead of inhibitory neurotransmitter. So over stimulation and other mental issues may arise from such an effect.

    That's pretty much the important things covered. But this is all very complex and there are other reasons for GABA to be low than having issues with GAD genes.

    What i do know is that persons in need of GABA can be somewhat helped by the GABA pre-cursor L-theanine which can be found in green tea as well.
     
    helen1 likes this.
  6. kraken

    kraken

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    I too wonder about the GAD1 gene. I'm actually heterozygous for 9 out of 11 SNPs listed from MTHFRSupport.com. Wonder if this could explain some of the anxiety which been arising more and more the last 6 years. I do wonderful on Gaba-agonists (who doesn't?) but thats not a long-term solution as down-regulation would leave you feeling even more anxious.

    I definitely can attest to the high Glutamate, low Gaba. Anyone digged deeper into this? Guess it could be very beneficial for people with GAD1 mutations to supplement with something that balances this out. A bit interested in NMDA-antagonists which seems to be good for excessive glutamate signaling. I tend to do pretty good on them too.
     
    helen1 likes this.
  7. Azrael

    Azrael

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    Well 9 hetero GAD1 genes have to mean it has some impact. It's different for me, I tried some of the recommended supplements like theanine and can now safely say it wont help me get better. There's other factors that plays a part in my health.

    The theanine supplements I tried had a heavy impact on me as glutamate went to the bottom and so did nor adrenaline. I have stopped using it for the time being. But very good to know it has such a big result dealing with high nor adrenaline and glutamate.

    In my experience following supplements have an antagonist effect on NMDA: Taurine, Glycine, Theanine and Curcumin. I have tried all 4 for testing purposes and if you get theanine to work I think that's the best thing you can take, afterall the japanese drink green tea almost every day :)

    Kraken have you tried theanine? From what I have read from other users there's not a down regulation feeling from taking theanine like there is for benzos etc. So if you have not - consider taking it on a spin.
     
    Paralee likes this.
  8. Valentijn

    Valentijn Senior Member

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    No it doesn't. To know if there's any impact, you have to read the research regarding each SNP.
     
  9. Azrael

    Azrael

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    That should always be routine to further your reading if you suspect this could be a problem. Nothing sensational with that.

    Kraken knows things about his own health that none of us knows about.
     
  10. MrME/CFS++

    MrME/CFS++

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    It MAY or MAY not, would be a better (polite) answer to that. Research does not say anything of the burden on the gene if there is more than one (in this case 9) mutation in it. If there is evidence for that, I want to know. I know there is for some rare "deseases", but not for every combinations out there.

    I asume that we all know that the total combination of genes in a person makes it unike. Mentaly, physically etc. Also combinations of mutations in each gene would therefore be unike, and expressed diffrently in each person.

    In my opinion every single SNP MAY have som kind of inpact on each person, and the combination of his mutations could have an patological inpact if the combination is not a good one. Nobody knows that for sure today.

    What really makes me sad is that researchers make their statements by researching people that have messed their lifes up with poisening all their life. From the day they bread their first oxygene, it start to put in whatever that smells and taste good. Human beeing are the only species on earth that think they can eat everything and go through their lifes without symptoms of it. Alcohole, sugar, grains, milk, drugs and you name it. its not even strange that we early in our lifes start to "feel" bad. Before we can make scientific evidence for this and that we should first start to research on healthy people, if there are one left. :) You can not say that this gene gives a person more chanse of a desease, when the real truth is that "with this gene you have got, you cant live like you have done up today". You have to give your gene what it was suposed to have. We cant supplement with nutritions because we want to go on with our wrong lifestyles. First step will be to fix that issue, and then we can start to play with genes that struggles to keep going normal. But everyone should know that it took X years before feeling sick, and it will take the same X years to be as quick as you where. Its not done in one week.

    The statement is brutal, but every forum I am into I feel that everybody is needing for a quick fix, and they dose theire medications/nutrition as if it where water. Its not that easy.

    I also have a lot of mutations in GAD1 gene, and 2 of them rarer than 3%. I know this gene is killing me, because all researching i have read fits me perfectly. Yes, I truely believe that if you got the symptoms that researcers have found for those 9 genes, it may well have some inpact on you all together. For me every medication that hits the GABAA or GABAB receptors does wonders in some variation. Everything else kills me. Too much GABA for a normal person wil NOT feel good. So everybody does not feel good om GABA medications.

    Low GABA will often manifest with more pain, stiffness, feeling of inner turmoil, anxiety. Severe low GABA could lead to stiff man syndrome wich is a rare autoimmune desease. GABA is calmness in both mental state and body generally.

    Neurontin (GABAA) and Baclofen (GABAB) has helped me before I got ME/CFS, after that I have not used it steady. I'm too sick to participate in social life, and wont use it if i dont need it. Those medications should be used in low doses over time, because they build up GABA over time. A dose that you almost not feel will be best. In my opinion. Yes, it will also be addictive over time as all GABA medicine is. I will start to try FMN (riboflavin variant) soon, as a last try to heal my GABA problems. Thanks to @ppodhajski for his studies and experience with that protocol.



    Well, thanks for listening. :D
     
    Last edited: Feb 18, 2016
  11. Valentijn

    Valentijn Senior Member

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    The statement was that the SNPs "have to" have an effect. They don't have to do any such thing.
    Yes, that's why it's necessary to read the research, as I said above.
    Well, your opinion is "interesting", but science disagree. And I'm afraid I trust the results of decades of methodological investigations by a lot of people a lot more than I trust someone's opinion.
    There's been plenty of genetic research on healthy people.
    Sorry, it doesn't work that way. The research controls for lifestyle factors related to the genes involved.
    Do you have a reputable citation which supports that rather unusual claim?
    And there are a thousand other things which could cause the same symptom. If you truly believe that GAD1 is "killing" you, there are doctors who can confirm that it is indeed the problem.
    "Belief" is not scientific. It is based on faith when there is a lack of evidence. You'd might as well believe that sitting down at the wrong time of day can cause the same symptoms.
    As will many other things. It doesn't make sense to fixate on a single cause, especially when there is no research showing those SNPs to have any impact.
    You're making a blind guess.
     
  12. Flo

    Flo

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    Hi,

    I have been reading these forums for a while and just joined. :)

    I am interested in GAD1 because glutamates in my foods seem to effect me so much.

    I think that we are all just experimenting here and should keep that in mind. Even with all the research on these SNPs doctors have no idea what is going on with us. I think as well that researchers do not usually look at all the SNPs in a gene when they are doing these studies and in that way we might be much further ahead of them. It could be that some people here might be way ahead of the research! But it is hard for me to say conclusively or not that GAD1 SNPs are good or bad since illness might pop up because of some GAD1 SNPs in combination with some SNPs in another gene that you might or might not have. But there has not been a lot of research on these SNPs to draw any conclusions on SNPs one way or another.

    I guess my question would be, have researchers looked at all of the GAD1 SNPs at the same time and compared them with enzyme activity? Connecting SNPs to illness to me is kind of the wrong way to look at this since illness might be dependent on several genes and GAD1 is just one of them. So in one group of people they might find no connection to illness and in another they find a direct connection. Ugh, I hope I am making sense here!

    I did find this that just showed that reduced GAD1 in combination with COMT issues might have some relation to schizophrenia.
    http://www.nature.com/mp/journal/v12/n9/abs/4001988a.html
    "Finally, we observed evidence of statistical epistasis between two SNPs in COMT and SNPs in GAD1"

    I read here a lot that sometimes a supplement might work for one person and not another, maybe that is the reason? I think if GABA makes someone feel better and they have low frequency GAD1 SNPs, it might be a clue regardless of the research, or lack of research.

    But doctors and research never helped me much so I do not depend on either of them!
     
    MrME/CFS++ likes this.
  13. bertiedog

    bertiedog Senior Member

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    I am homozygous for 2 of the GAD1 genes and I have suffered with horrendous migraines since I was 20. Basically I have tried everything to get them under control but they have got worse and worse and have ended up almost daily.

    However at last it looks like I have found something that is getting them under control. Within an hour of the morning migraine and taking 25 mg Pregabalin (Lyrica) it starts to lift. This has happened 3 mornings in a row now so I looked up why it might be that this is working for me and there is a connection I believe to GAD1 because Pregabalin works on boosting the connection or break down of glutamic acid into GABA. I understand that GAD1 can mess up the break down of glutamic acid so one can end up with too much glutamate.

    Lyrics is prescribed for epilepsy which is interesting because in the 70s I believe Oliver Sachs wrote about the connection between epilepsy and migraine but I haven't come across this idea more recently.

    I had worked out before that glutamate was an issue in my migraines because of the negative effect any form of extra folate has on me. I end up with non stop migraine every time I take any form of folate apart from what is in my food.

    I am just keeping my fingers crossed that the Headache Consultant that I see through the NHS will be happy to let me have a good long trial of it because it has been pointed out to me that it is quite an expensive drug. However nothing else has worked to prevent these horrendous migraines so I don't have any other options.

    Pam
     
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  14. Valentijn

    Valentijn Senior Member

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    Do you mean you are homozygous for 2 SNPs on the GAD1 gene? Which SNPs are they, and is there research indicating that they are problematic? Most SNPs have no impact at all, and simply being homozygous is irrelevant.
     
  15. bertiedog

    bertiedog Senior Member

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    From Wicki regarding Pregabalin

    Pregabalin is a GABAergic anticonvulsant and depressant of the central nervous system (CNS). It is classified as a GABA analogue and gabapentinoid.[47]It is a close analogue of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).[48][49][50][17] Pregabalin binds with high affinity to the α2δ subunit-containing voltage-gated calcium channels (VDCC). It increases extracellular GABA concentrations in the brain by producing a dose-dependent increase in L-Glutamic acid decarboxylase (GAD), the enzyme responsible for making GABA.[51][51][52][53]

    Yes I am homozygous for 2 SNPs on the GAD1 enzyme so having read the above information I think you will agree it is highly likely that the connection I made is entirely possible.

    Pam
     
    Last edited: Jan 15, 2017
  16. Valentijn

    Valentijn Senior Member

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    The GAD1 gene creates the GAD enzyme. But SNPs (single alleles) on the GAD1 gene control how the enzyme is formed. It's the SNPs which can cause the GAD1 gene to have problems, but only specific SNPs can do that. Most variations of SNPs that people have on GAD1 won't make any difference in the enzyme that is created.

    But being "homozygous" is quite meaningless in determining if the SNP can cause problems. The specific SNP itself has to be capable of causing problems, usually shown in research, or by algorithms which make predictions based on what is known about SNPs in general and whichever gene they are located on.

    So to determine if a SNP can cause problems, you need to get the "rs" number for it and look up the research or a reliable summary of the research. SNPedia is a decent resource to start with (though not always correct), and both summarizes and links to the research.
     
  17. bertiedog

    bertiedog Senior Member

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    In general I understand what you are saying @Valentijn but I think you also have to take on board apart from published research various practitioner's experience of dealing with many patients who have various SNPs and how they can appear to cause certain problems. If they find that there is a correlation between various SNPs and health issues that their patients have I don't see how it is beneficial to ignore their findings.

    In my case all that matters is that the lowest possible dose of Pregabalin helps to stop my unremitting migraines and the fact is that Pregabalin works on the GAD enzyme. I have 2 SNPs in this enzyme that might or might not affect how it works. I fail to see how a connection cannot be made between these 2 facts but I don't intend to go further into this with you.

    Pam
     
  18. Paralee

    Paralee Senior Member

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    I think I'd better go to another section, haha. I have 4 GAD1 homozygous, haven't checked them out though. I just checked my livewello and saw them.
     
  19. Gingergrrl

    Gingergrrl Senior Member

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    Do any of you in this thread test positive for autoantibodies for GAD65?

    I have anti GAD65 Abs on multiple tests (from Mayo & Quest) and I had an insanely high startle reflex for about two years and a possible startle seizure to our fire alarm several months ago.

    I was also starting to have incidents that resembled SPS (Stiff Person Syndrome) after being startled by something as basic as a knock on door or my dog barking. The muscle dystonia, and shot of adrenaline to the heart feeling, could last for minutes or up to 48 hrs.

    After I started IVIG, all of it disappeared and remains completely gone. I've since experienced our fire alarm going off, and other major startling triggers, with no reaction. The entire thing is gone but whether temporary or permanent, I have no idea!

    I have other issues that are not gone but the ones connected to GAD65 are gone. I have also always done well with benzos and meds that increase GABA but some of those also block the calcium channels (my other autoantibody) so I have to be careful with them.
     
    Last edited: Jan 24, 2017
  20. Valentijn

    Valentijn Senior Member

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    I'm being tested, after my presumed Type 2 diabetes diagnosis from last week was followed by protracted hyperglycemia, ketonuria, nasty headaches, and diarrhea. I should have the results in a few weeks.
     
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