1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
ME/CFS: A disease at war with itself
We can all agree that ME/CFS is a nasty disease, particularly in its severe form, but there are abundant nasty diseases in the world. What is unique and particularly confounding about our disease is that so much controversy surrounds it, and not only surrounds it, but invades it too.
Discuss the article on the Forums.

Altered sympathetic reactivity & norepinephrine transporter expression in POTS

Discussion in 'Problems Standing: Orthostatic Intolerance; POTS' started by Allyson, Jan 31, 2014.

  1. Allyson

    Allyson *****

    Messages:
    1,684
    Likes:
    669
    Australia, Melbourne
    medical article on POTS

    CONCLUSIONS: Patients with POTS exhibit a decrease in NET protein in their peripheral sympathetic nerves. Paradoxically, whole-body NE spillover to plasma during rest in the supine position and in response to head-up tilt is not altered despite excessive nerve firing rate in response to the head-up tilt.

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

    A
    Last edited by a moderator: Jan 31, 2014
    alex3619, Valentijn and aimossy like this.
  2. Valentijn

    Valentijn Activity Level: 3

    Messages:
    6,128
    Likes:
    8,566
    Amersfoort, Netherlands
    I had a quick look at the gene which produces NET, SLC6A2, to see how rare the SNPs are for ME/CFS patients. Purple = 0 - 1% prevalence for that genotype, red = 1 - 2.5%, orange = 2.5 - 5%, and yellow = 5 - 10%. Items with a bolded and underlined RSID have research associated with them.

    SLC6A2.gif

    So 4 of us have some pretty rare genotypes, and a couple more have multiple less-rare genotypes, compared to just one control showing much rareness.
    SOC and MeSci like this.
  3. bel canto

    bel canto Senior Member

    Messages:
    188
    Likes:
    170
    rs168924
    rs2242446
    rs3785143
    rs17247999
    rs17841329
    rs187715
    rs36023
    rs3785152
    rs40147
    rs12443955
    rs10521329
    rs880711
    rs3785157
    rs5568
    rs1566652
    rs8047672
    rs5569
    rs998424
    rs36009
    rs1800887
    rs36007
    rs15534
    rs42460
    rs7194256
    rs10521330

    The plug -n for firefox doesn't work for the snp's in the data tables, so I'm retyping them in the hope that the plug-in will work for these.
    Valentijn likes this.
  4. alex3619

    alex3619 Senior Member

    Messages:
    7,064
    Likes:
    10,906
    Logan, Queensland, Australia
    Probable mechanism. However, why is this happening? Genetics may explain increased vulnerability, but I am not yet sure that is the whole thing. One thing I would really want to see is staining for enteroviruses in the same veins they are testing for norepinephrine transporters. It would also be interesting to investigate for antibody issues with this tissue.

    According to Wikipedia, one associated gene defect in NET is linked to orthostatic intolerance. http://en.wikipedia.org/wiki/Norepinephrine_transporter

    It would be interested to see if the same NET problem is also present in non-POTS ME patients with OI.

    A NET defect is also probably responsible for considerable cognitive problems. If this is found in ME with or without POTS, it may directly explain many of our symptoms. It still leaves why this is happening unexplained.
    voner, Valentijn, SOC and 1 other person like this.
  5. Valentijn

    Valentijn Activity Level: 3

    Messages:
    6,128
    Likes:
    8,566
    Amersfoort, Netherlands
    It won't let me upload excel sheets, so these are screenshots.
  6. Valentijn

    Valentijn Activity Level: 3

    Messages:
    6,128
    Likes:
    8,566
    Amersfoort, Netherlands
    That SNP isn't tested by 23andMe.
  7. Jackie M

    Jackie M

    Messages:
    12
    Likes:
    11
    Illinois USA
    Bummer!

    The POTS doctor at Mayo said having a NET deficiency likely isn't an issue for me since my supine serum norepinephrine is normal and my standing norepinephrine skyrockets (increases five-fold). He said if I had reuptake issues, he would expect my supine levels to be high from when I stood prior to laying down (30 minutes in dark room) for the blood draw. Still: I was curious and hoping I would luck out and it would be tested by 23andMe.

    I now know the SNPs tested by 23andMe on that gene aren't "the" SNP, but looking at my Promethease report, I have somewhat rare mutations on that gene at:
    rs10521329 AA
    rs2242447 CC
    rs15534 TT
    Last edited: Aug 13, 2014
    Valentijn likes this.
  8. Valentijn

    Valentijn Activity Level: 3

    Messages:
    6,128
    Likes:
    8,566
    Amersfoort, Netherlands
    @Jackie M - The first and last ones you listed are pretty rare when homozygous, but the middle one is extremely common.
  9. Jackie M

    Jackie M

    Messages:
    12
    Likes:
    11
    Illinois USA
    @Valentijn -- Promethease reports the rs2242447 CC genotype occurs in 8% of Europeans according to their pool of genes, however I see in other populations, it is much more common. They only have 180 people for their European pool though, so it often can be very misleading.
    http://www.snpedia.com/index.php/Rs2242447
    MeSci likes this.
  10. Valentijn

    Valentijn Activity Level: 3

    Messages:
    6,128
    Likes:
    8,566
    Amersfoort, Netherlands
    Yes, I don't think that using small samples from a specific ethnic group is constructive at all.
    Sushi and MeSci like this.
  11. est_sunshine

    est_sunshine

    Messages:
    27
    Likes:
    23
    The thing about this research that hit home to me, is that norepinephrine as an amine is competitively taken up with other amines, like histamine and tyramine. So this explains a lot about why a low amine diet/lifestyle is helping my POTS - the fewer amines in the system, the easier it is for the body to use the transporters it has. I think the reason the transporters are not working correctly relates to autoimmunity, which stems from bad balance of gut bacteria and hence overactive immune response. So now I'm trying to eat more unwashed herbs from my garden. They're also natural antihistamines so hopefully that will help too. Or I'll get ecoli and worms! Some people think this might be a good thing!

See more popular forum discussions.

Share This Page