Gene Possibly Links Stress, Immune Dysfunction and Infection in ME/CFS

[Cort]

This is a complex and fascinating study. It linked a variant of the COMT gene - which effect the levels of a large number of important neurotransmitters and catecholamines including dopamine, norepinephrinne and epinephrine - to a possibly important but little discussed immune dysfunction in ME/CFS - low IgG 3 levels - PLUS increased IgE (allergy?) levels - and upper respiratory infections...That's a pretty good correlation!

Several ME/CFS and FM doctors have said they believe low IgG 3 subclass levels are associated with small fiber neuropathy in FM.

In any case this study suggests a genetic predisposition to immune dysfunction in ME/CFS may be present.

J Transl Med. 2015 Aug 14;13(1):264. doi: 10.1186/s12967-015-0628-4. Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients withchronic fatigue syndrome. Löbel M1, Mooslechner AA2, Bauer S3, Günther S4, Letsch A5, Hanitsch LG6, Grabowski P7, Meisel C8,9, Volk HD10,11, Scheibenbogen C12,13.


BACKGROUND:
Chronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients suffer from sustained exhaustion, cognitive impairment and an increased sensitivity to pain and sensory stimuli. A subset of patients has frequent respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous system and an association with genetic variations in the catechol-O-methyltransferase (COMT) and glucocorticoid receptor genes influencing sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed the prevalence of SNPs of COMT and glucocorticoid receptor-associated genes in CFS patients and correlated them to immunoglobulin levels and susceptibility to RRTI.

METHODS:
We analyzed blood cells of 74 CFS patients and 76 healthy controls for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum immunoglobulins were determined by immunoturbidimetric technique, cortisol levels by ECLIA.

RESULTS:
Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced cortisol levels providing evidence for its functional relevance. Both enhanced IgE and diminished IgG3 levels and an increased susceptibility to RRTI were observed in CFS patients with the Met/Met variant. Such an association was not observed in 68 non-CFS patients with RRTI.

CONCLUSION:
Our results indicate a relationship of COMT polymorphism rs4680 with immune dysregulation in CFS providing a potential link for the association between stress and infection susceptibility in CFS.

 

[Zapped]

Cort's been sleuthing in the remoteness; watch out for the Mamba...

Great stuff! This is where my personal speculation/interest lies.

While the research terminology is specific to those needing such specificity the concept is key, IMO. Stress, like art is hard to quantify and each of us requires a unique exposure of each before an affect results. An hypothesis is, that once this threshold is reached (or maxed out,⎇,) the system capacity for such is full; any more is like a cup running over which triggers a release of epinephrine (or other affecting hormone) into the system which in turns spreads to wreak the many havocs known (and unrecognized as yet). ...Don't most PWC's report such stress prior to a crash... ?

I hope some momentum will grow from this study into other research.

Thanks, and please publish more as you come across it.

 

[Cort]

Watch out for the mamba!

I like it!

I agree -at some point our cup runneth over...

 

[Grace2U]

Please do Cort.....publish more of this as you find it . My Neuro said both my IgA and IgG levels were low yet he doesn't think it's elevent to my symptoms....⁉️⁉️⁉️ (Don't know if he tested the M E or D.) I'm going to ask him about this study as well as pull up any info I can find about the COMT gene on my "23 and me" results.

I'm with "Zapped"...... No doubt all stressors, physical, mental, and emotional, promote crashes. Interesting..."our cups running over triggers the release of epinephrine or other hormone..." Thank you Zapped

 

[kevin Feldman]

does anyone know where to get raw genetic info analyzed for snp's?

 

[Zapped]

does anyone know where to get raw genetic info analyzed for snp's?

Have you looked here per other's post:

https://genesforgood.sph.umich.edu/

 

[kevin Feldman]

This is a complex and fascinating study. It linked a variant of the COMT gene - which effect the levels of a large number of important neurotransmitters and catecholamines including dopamine, norepinephrinne and epinephrine - to a possibly important but little discussed immune dysfunction in ME/CFS - low IgG 3 levels - PLUS increased IgE (allergy?) levels - and upper respiratory infections...That's a pretty good correlation!

Several ME/CFS and FM doctors have said they believe low IgG 3 subclass levels are associated with small fiber neuropathy in FM.

In any case this study suggests a genetic predisposition to immune dysfunction in ME/CFS may be present.

X another one off on the checklist. I just got back my genome raw data from 23andme. I search for comt snps and look what I found!! View attachment 638

 

[kevin Feldman]

Have you looked here per other's post:

https://genesforgood.sph.umich.edu/

Thanks yes it was in FAQ-they are working on it I already have the data
"
Is it possible to upload Whole Genome Sequencing (WGS) files in addition to 23andMe files? If yes, do you have preference for data formats?

We are curious about allowing this, and will have to figure out how to gauge how many people would be interested in donating / sharing their data in this way. In the short term, a VCF file seems appealing (a BAM/CRAM would provide the most long-term flexibility but might be cumbersome to transfer)."

 

[kevin Feldman]

Have you looked here per other's post:

https://genesforgood.sph.umich.edu/

There are about avg 2,000 genes per chromosome. I just counted 22 COMT snps and 67 MTHFR snps. Is that alot? U guess so I must have zillions of snps , no wonder I feel so rotten