Genetics: Chromosome 6 BTN2A2 and BTN3A3 (BTN2A1)

Hoopoe said:
Now that I've improved, I'm able to do sports, but am still limited by something that I can only describe as exertion intolerance (where exertion includes mental exertion). I've been able to train enough to improve my peak performance and do sports but a defect still persists, where the following days tend to be unpleasant and unproductive.
Click to expand...
This was exactly what my prodrome phase was like -- though at the time, of course, I didn't think I was sick and just gradually developed the belief that it was normal to be useless for 3 days after a jog and started arranging my exercise to be long before or after other important commitments.

Agree that the ratcheting down feels like a failure to recover. Wish we knew more about what that means in the brain.
 
Last edited:
ScoutB said:
This was exactly what my prodrome phase was like -- though at the time, of course, I didn't think I was sick and just gradually developed the belief that it was normal to be useless for 3 days after a jog and starting arranging my exercise to be long before or after other important commitments.

Agree that the ratcheting down feels like a failure to recover. Wish we knew more about what that means in the brain.
Click to expand...
This sounds a lot like my prodrome phase, although I never did much formal exercise in that time. But I always felt fried after socialising (nights out took ages to recover from but even just hanging out with mates) or a full day of lectures and seminars etc.

One of the things I remember from that time is how I would consistently get insomnia after e.g. a bartending shift or a night out, to the point of not sleeping until way past dawn, sometimes until mid morning the next day or later. Which now really seems like a tired but wired thing.

So I was definitely not healthy but I don't remember getting anything I can point to definitively as PEM in that time. Maybe during bad hangovers but its so hard to tell. Nothing like my first major incident of PEM I remember, where I had to sit down for a while in Glasgow uni library and couldn't keep my eyes open, feeling ill and lethargic and like a leaden weight was keeping me in the chair.
 
Last edited:
I used to say that my body feels like a flywheel without brakes. If you get the wheel spinning, the momentum is going to keep it going for a long time. If it goes too fast, it’s going to tear itself to pieces. Keeping the wheel spinning will wear the machine out, there’s no time for maintenance.

It reminds me a bit of sleep deprivation.
 
ChronicallyOverIt said:
This got me thinking, is there a way to link this to @DMissa newest paper? Would the lipid accumulation seen in that paper trigger the BTN2A1 or BTN3A1, thus triggering the T-cells?
Click to expand...
Don't know. Hard to compare observation made with immortalised cells in culture medium with primary cells in peripheral blood. With follow up work maybe we can think about this but I wouldn't run away with it yet
 
That proteomic study with very noticable "non response" pattern to exercise might be the closest someone has ever gotten to the core of the failure to recover defect.

What could possibly cause a, presumably widespread, failure to shift protein expression towards facilitating recovery state? It has to be a metabolic defect or a failure to orchestrate this response due to a weak/bad signal.

The main effect seems to be a delayed so it looks like it's something that occurs during the later stages of recovery. Maybe a hormone or immune problem or something to do with waste removal during sleep.
 
Last edited:
Hoopoe said:
Presumably the defect in ME/CFS is in a part of physiology that has been overlooked so far, or isn't well understood or easily measurable.
Click to expand...
This is maybe a silly thought but should we have a thread of areas of biology/physiology that meet this criteria that could be worth having a think about? People could post papers and if anything deserves its own thread it could sort of branch off.

Just a thread for kicking around ideas of 'oh this kind of signalling in this tissue' and 'what about this region of the brain' that might not be developed enough for their own thread.
 
Jonathan Edwards said:
I note that BTN2A1 variants confer risk for systemic lupus. That might be an important clue.
Click to expand...

When I was looking yesterday I saw links to spondylitis too, though the genetic burden seemed low (0.3 out of 1.0). But in polygenic disease that could be quite high – hard to know.

ETA: found the page again.

platform.opentargets.org

Open Targets Platform

The Open Targets Platform integrates publicly available datasets to support systematic identification and prioritisation of drug targets.
platform.opentargets.org platform.opentargets.org
 
forestglip said:
decodeme-sle-chr6:24539176-34239176.png
Click to expand...
That's near the BTN2A1 locus for lupus and ME/CFS (not all genes shown). The ME/CFS locus is a little red hill on the left near the value 26.

It seems that for lupus, the main thing here is a gene farther to the right. Maybe an HLA gene. Though it's possible the BTN genes are also contributing to the significance towards the left
 
forestglip said:
It seems that for lupus, the main thing here is a gene farther to the right. Maybe an HLA gene. Though it's possible the BTN genes are also contributing to the significance towards the left
Click to expand...

Yes, the lupus plot looks too complicated and mostly far to the right. Maybe lupus isn't a clue here.

A link to spondarthropathy would be interesting in that for a long time I thought Reiter's spondarthropathy was perhaps the most likely clue to a model for an immune response driving ME/CFS.
 
This might be relevant. I don't understand the significance for EBV induced tumours but they maybe doesn't matter.

Int J Mol Sci 2024 Dec 15;25(24):13452.
doi: 10.3390/ijms252413452.

Epstein-Barr Virus BRRF1 Induces Butyrophilin 2A1 in Nasopharyngeal Carcinoma NPC43 Cells via the IL-22/JAK3-STAT3 Pathway​

Yue Liu <a title="Medical School, Fuyang Normal University, Fuyang 236000, China." href="https://pubmed.ncbi.nlm.nih.gov/39769218/#full-view-affiliation-1">1</a> <a title="Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China." href="https://pubmed.ncbi.nlm.nih.gov/39769218/#full-view-affiliation-2">2</a>, Ka Sin Lui <a title="Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China." href="https://pubmed.ncbi.nlm.nih.gov/39769218/#full-view-affiliation-2">2</a>, Zuodong Ye <a title="Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China." href="https://pubmed.ncbi.nlm.nih.gov/39769218/#full-view-affiliation-2">2</a>, Luo Chen <a title="Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China." href="https://pubmed.ncbi.nlm.nih.gov/39769218/#full-view-affiliation-3">3</a>, Allen Ka Loon Cheung <a title="Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China." href="https://pubmed.ncbi.nlm.nih.gov/39769218/#full-view-affiliation-2">2</a>
Affiliations expand
 
There seems to be an association between BTN2A1 and dyslipidaemia / hypercholesterolaemia / type II diabetes. Most of the papers I've come across so far have been in East Asian cohorts, but worth considering that this may be a confounder as well -

Association of a polymorphism of BTN2A1 with dislipidemia in community-dwelling Japanese individuals
Association of a polymorphism of BTN2A1 with type 2 diabetes mellitus in Japanese individuals

Tangentially: while looking for information on the AZ dataset, I also noticed that raw summary statistics for UK Biobank CNV & WGS PheWAS performed by AZ are available for public download - Link - Bulk Data Downloads.
 
You must log in or register to reply here.
Back
Top Bottom