Altered sympathetic reactivity & norepinephrine transporter expression in POTS

[Allyson]

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

 

[Valentijn]

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.

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.

 

[bel canto]

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.

 

[alex3619]

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.

 

[Valentijn]

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.

It won't let me upload excel sheets, so these are screenshots.

 

[Valentijn]

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

That SNP isn't tested by 23andMe.

 

[Jackie M]

That SNP isn't tested by 23andMe.

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

 

[Valentijn]

@Jackie M - The first and last ones you listed are pretty rare when homozygous, but the middle one is extremely common.

 

[Jackie M]

@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

 

[Valentijn]

@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.

Yes, I don't think that using small samples from a specific ethnic group is constructive at all.

 

[est_sunshine]

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!

 

[xks201]

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!

Or the bacteria are producing substrates that compete with norepinphrine for the transporters. just an idea lol

 

[xks201]

I have rs3785157 TT(red) and rs998424 AA (yellow) mutations. I don't know nor do I know if anyone knows to what extent these mutations make the norepinephrine transporter dysfunctional. That would be nice to know but research looks like it just shows an ADHD association. lol

 

[Never Give Up]

Huh?

 

[xks201]

referring to the chart posted in the thread regarding this indicating severity with the color codes. alleles..genetics..

 

[JaimeS]

Lots of things can cause POTS, and NET deficiency is one.

-J