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Autism SNP's, Interferon, & Chemokines

Discussion in 'Genetic Testing and SNPs' started by LaurieL, Jan 17, 2013.

  1. LaurieL

    LaurieL Senior Member

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    I would like to start this new thread so as not to completely hijack KDay's thread on geneticgenie. I also think Autism is absolutely related to CFS/ME, as some of the principles and treatments associated with ASD have worked so very well for me personally.

    Kday posted testing SNP's relating to Autism in which I investigated my own results at 23andme. Natasha posted related Interferon and chemokines associated with those with ASD. My investigations were intersting in that my results correlated with the information the both of them presented. I have copied some of their posts here to start the thread. Thank you both for this avenue.

    There were 36 total SNP's for females. My results include:

    (14) Dominant = 8(+/+), 3(+/-)
    (11) Recessive= 4(+/+), 4(+/-)
    (11) Additive= 7(+/+), 2(+/-)

    Total (+/+) = 19
    Total (+/-) = 10
    Total (-/-) = 6
    NoCall= 1

    I went to 23andme, in the Interferon genes or IFNA, I had quite a few results in which NO GENE FOUND was recorded. Whether that is due to deletion as stated in Natasha's quote, or whether 23andme did not test for it, I do not know. None the less, it is interesting for a follow up. The interferon genes are quite specific in 23andme, and only one result is given for each. I do not believe there is a risk allele associated with the INFA and correlating number. But for the chemokines, there are several SNP's listed and of which I am missing information on risk alleles to make an assessment of the SNP's listed.

    Natasha, anyone, do you have the risk alleles associated with these SNP's?

    There are ten (10) IFNA's listed. Out of those 10, I only have 3. 7 out of the 10 came back as NO GENE FOUND.

    Here is a list of what was mentioned in Natasha's post and source quoted. I have included the SNP rs#'s except for those genes that were not found in my DNA profile for IFNA.

    NGF= NO GENE FOUND

    IFNA10 rs 12555631
    IFNA2 rs10120977
    IFNA14 NGF
    IFNA22 NGF
    IFNA4 NGF
    IFNA5 NGF
    IFNA6 NGF
    IFNA7 NGF
    IFNA8 rs16938396
    IFNA17 NGF

    As an aside, this would explain why my projected response to interferon treatment should I contract hepatitis would be compromised as stated in my 23andme profile.

    The following is where I need risk alleles... (or is the "gain of copies in the c-c motif they refer to?)

    CCL1 rs3136682
    CCL1 rs2282692
    CCL1 rs159271
    CCL1 rs3138032

    CCL11 rs1129844
    CCL11 rs1860184
    CCL11 rs3815341
    CCL11 rs4795898
    CCL11 rs1019109

    CCL13 rs3136677
    CCL13 rs159313

    CCL2 rs2857657
    CCL2 rs4586
    CCL2 rs13900

    CCL17 rs3091237
    CCL17 rs3091321

    CCL8 rs3138036
    CCL8 rs1133763

    Again, thank you for all of this.

    LaurieL
  2. LaurieL

    LaurieL Senior Member

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    An example of intestinal dysbiosis and the ability of bacteria to suppress interferon. With interferon interference, white blood cells would be low even in the presence of infection. Cytokines activated and protracted.

    http://www.ncbi.nlm.nih.gov/pubmed/12525001

  3. Research 1st

    Research 1st

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    Hi Laurie L

    Do you know if people with ME or CFS report increased rates of Autism in their blood related families? I wonder if any research or discussions have been had on this matter?
    I'd love to know.

    Certainly when I read people interested in the biology of Autism I notice a similar inflammatory profile associated to what is called CFS. (Chemokines and TH1/TH2 profile).

    Looking at the most recent ideas on Autism, scientists now propose that Autism is not just a 'genetic' problem but more of an environmental issue I think. E.g. what we come into contact with in society.

    What seems to be preventing this information getting out is the apparent ease of which children are diagnosed as being Autistic not because they have developmental Autism and retardation (Autism is within the category of mental retardation, e.g. delayed developmental learning) but because they have behavioural problems, ADHD and are a little 'Aspie' in nature.

    So Autism is being diluted by psychiatrists meaning its getting hard to propose a neuroimmune disease model for Autism.

    I like this website, have you seen it?
    https://www.stopcallingitautism.org/


    Their front page says: ''Evidence indicates that children with autism suffer from an ongoing neuroinflammatory process in different regions of the brain involving microglial activation.
    Microglial activation result in a loss of connections between the neurons reducing their function and leading to what is known as autism.''

    I thought that was interesting as 'CFS' (ME) also can involve micro-glial activation if one measures blood chemokines and/or is fortunate to have a PET scan.

    Thank you.
  4. LaurieL

    LaurieL Senior Member

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    Hello R1,

    There have been several "mentions" on this forum, and some references, in which interested me enough to follow up on, plug in my data, and see how it compared. With my own experiences, these were some of the most effective treatments I received, and these were derived from Autism treatments. I was working from both communities (Autism and CFS/ME) with the mind set that yes, they have very similar immunological profiles and resulting cascades there in. I was also asked to take a research study survey by 23andme in which then piqued my interest further. (The fact that they would have this survey, would lend a certain air, don't you think? I also have the classical profile for CFS.

    On another note, as far as my family. Nobody officially diagnosed to my knowledge. We did suspect my brother to have Aspberger's. And now that I think about it, I think my mother would have been a good candidate. As far as myself growing up, it was never suggested, or presented, or mentioned. Not one thing about my mother either. But there is a certain presentation, and she fits it. It explains a lot to me. (There is a 23 year difference between the brother I reference and myself). I remember the doc's suggesting that perhaps it was a result of the age in which she had him, 43. But now,...I don't think so.

    I agree on the cytokines, but I have seen both Th1 dominance, and Th2 dominance, and swings back and forth as well.

    I cannot agree with you on this one. I believe they stick this label on this type of research, for two reasons. 1) To support a psychological diagnosis (because if it is strictly environmental, then the prospect of finding those elements are impossible, thus lack of funding), and 2) to account for the huge upswing in the occurrence of Autism. Yes, the pool is diluted with other conditions, such as the ADHD, etc; but if they really did a comparison of the genetic mutations, I believe that dilution would cease.

    Mental retardation has differing degrees and affects. The same with Autism, in that Aspberger's and ADHD have similar profiles. What they don't know is whether it is due to the differences/similarities in environmental exposure and/or genetic mutations, or both. Hence the investigations into the environmental aspect. Of which I believe will not be the sole determining factor of the occurence, much less the spike in diagnoses. And the spike is occurring around the world. I think it is a great disservice to label this spike as correlating with an increase in environmental exposures. If genetics didn't have anything to do with it, then every blood line would succumb to one of these. There is no way environment can explain the spike,.....well, there might be one thing, but onward.

    Every chronic disease out there is being labeled as psychiatric. There's a lot of pills to be given out, and a lot of money to be had.

    No, I haven't but I will go check it out. And yes, I find that interesting as well.

    Nice to meet you, and thank you. I appreciate the response. It saved me from talking to myself on this thread.

    LaurieL
  5. LaurieL

    LaurieL Senior Member

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    Interesting, but it doesn't state why the microglial activation takes place. Being a part of the immune system response, what sets it off? You know, I have seen many times, that the connections to Autism, ASD's, FMD, Alzhiemers, and others like diabetes and Thyroid problems, are G-proteins and GAG's. I propose that the G-proteins and GAGS could go one step further in saying that these all have acquired glycosylation abnormalities of proteins. Acquired glycoprotein disorder, not CGD.

    LaurieL
  6. LaurieL

    LaurieL Senior Member

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    I found this interesting...

    http://journals.cambridge.org/abstract_S1740925X12000142



  7. LaurieL

    LaurieL Senior Member

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    Here is some of the reasoning in why I am of the opinion that limiting the neuroinflammation to environmental causes or pyschological disease cannot be narrowed such that one generality can account for.

    NFKappaB

    Its triggers are known to be either environmental, endogenous, or infectious. These triggers include, "stress", Radiation, Oxidative Stress, Injury, Bacterial LPS, Viral Infections, Leaky gut and bacterial translocation, Food allergies, Environmental allergies, Diets high in macronutrients(Sugars, Lipids, and Proteins), Nutrient deficiencies, and Arachnidonic Acid Metabolites, to name a few...

    These lead to activation of NFKappaB.

    Which then leads to genetic expression for genes coding for pro-inflammatory and anti-apoptic cytokines.

    Which then leads to cytokine production, the production of adhesion molecules, and pro-inflammatory enzymes.

    The following seven listed occur along this pathway. Those seven being the production or induction of:

    1) IL-6 = CRP
    2) COX2 = Prostaglandins (PGE2) and/or Thromboxanes
    3) IL-1 = Collagenase/MMP
    4) Lipooxygenase = Luekotrines
    5) iNOS = NO
    6) TNF-a
    7) Adhesion molecules

    And of which all lead to negative feedback loops, which are incredibly hard to break, once they start. Which is why a cytokine storm is so incredibly hard to control and the treatment is palliative and supportive.

    These negative feedback loops then lead to more IL-1 and PGE2, ROS and oxidative stress, and more TNF-a and CRP. Viscious little cycle, and genetics absolutely play a part. As the triggers are highly variable and modifiable, and the genetic expression from one individual to another is as well.

    All of this then leads to pain, inflammation, cardiovascular disease, neurodegeneration, Insulin resistence, Autoimmune disease, Rheumatic disease, and yes.....cancer too.

    So compared to the controls considered normal, and those with Autism with higher then normal levels of microglial activation, and then those of us with CFS/ME, what predisposition exists, and do they differ with the trigger? How come I have been functional albeit I have had trouble with infections my entire life, but functional up until a certain point, and then I was knocked flat.
  8. LaurieL

    LaurieL Senior Member

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    I have always had one question in my mind. Were the mutations that we see now, in our results, were they there at birth as well? What about those kids with early diagnostic Autism?
  9. triffid113

    triffid113 Day of the Square Peg

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    On your list of cytokines in a viscious cycle, you list TNF-alpha and I wanted to say that DHEA has a significant impact of breaking that viscious cycle. This is according to www.lef.org. I find it helps me tremendously. I take 75mg/day and it 'corrects me' - I can feel it (very good) within 15 min and I also feel very bad w/o it.I also take very high antioxidants (2g C/day, 1g E/day). And I take 1g olive leaf extract to prevent gut pathogens (and the need for antioxidants against those).
  10. Lotus97

    Lotus97 Senior Member

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    I seem to have Asperger's syndrome. At least 2 online tests I took say I have Asperger's (albeit a mild case). I think the tests are as accurate a therapist or psychiatrist's diagnosis. I started a blog a few weeks ago with some multimedia resources and links to the online tests.
    http://forums.phoenixrising.me/inde...ist-introvert-add-adhd-ocd-neurotypical.1381/

    I was curious about Asperger's SNPs and I found they did a study comparing SNPs of people with Asperger's to people with other forms of autism.
    http://www.sciencedaily.com/releases/2009/07/090715101427.htm
    Asperger Syndrome, Autism, And Empathy: Study Links 27 Genes

    The research found that single nucleotide polymorphisms (SNPs) in 27 out of the 68 genes were nominally associated with either AS and/or with autistic traits/empathy. 10 of these genes (such as CYP11B1) were involved with sex steroid function, providing support for the role of this class of genes in autism and autistic traits. 8 of these genes (such as NTRK1) were involved in neural growth, providing further support to the idea that autism and autistic traits could result from aberrant patterns of connectivity in the developing brain. The other 9 genes (such as OXTR) were involved in social behaviour, shedding light on the biology of social and emotional sensitivity.

    Dr Chakrabarti commented: "These 27 genes represent preliminary leads for understanding the genetic bases of AS and related traits, such as empathy, in the general population. All of these are good candidates for independent replication studies in both low and high functioning autism samples. 5 of the genes we found have been previously reported in autism, but the other 22 have never before been reported in association with AS, autistic traits or empathy. We now need to test models of how these genes interact and construct 'risk' models for the development of AS."

    Professor Baron-Cohen added: "We chose to look at the genetics of AS because all other genetic studies have focused on classic autism, which can include learning difficulties and language delay. AS is a more 'pure' condition because these other factors are absent. These new results represent a significant advance over our previous work in showing that the sex steroid hormones (e.g. testosterone and oestrogen) influence social development and autistic traits. The new study also confirms earlier reports that other molecules (such as oxytocin) are important in understanding autism, autistic traits, and empathy."

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