Daytime Sleepiness maybe related to Narcolepsy gene

pattismith

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99% of narcolepsy + cataplexy patients carry the HLA DQB1*0602 allele.

89% of narcolepsy alone patients carry it.

25% caucasian healthy people carry it.

Narcolepsy is not ME/CFS, the question is more about the effect of the narco gene on healthy carriers and ME/CFS patients who carry the gene.

An old study found 43% of Fibro/ME/CFS patients were carriers for the allele, so it might be that it could impact our clinical picture.


During baseline, although DQB1*0602-positive subjects were subjectively sleepier and more fatigued, they showed greater sleep fragmentation, and decreased sleep homeostatic pressure and differentially sharper declines during the night (measured by non-REM EEG slow-wave energy [SWE]).


Conclusions:

DQB1*0602 positivity in a healthy population may represent a continuum of some sleep–wake features of narcolepsy.

DQB1*0602 was associated with interindividual differences in sleep homeostasis, physiologic sleep, sleepiness, and fatigue—but not in cognitive measures—during baseline and chronic Partial Sleep Deprivation.

Thus, DQB1*0602 may represent a genetic biomarker for predicting such individual differences in basal and sleep loss conditions.
A Retrospective Review of the Sleep Characteristics in Patients with Chronic Fatigue Syndrome and Fibromyalgia - Spitzer - 2010 - Pain Practice - Wiley Online Library

DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue (nih.gov)
 

Alvin2

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This is an incongruous result as narcolepsy is believed to be caused by destruction of orexin producing cells. If those cells are intact then you don't have narcolepsy. And presumably this allele increases the likelihood of the autoimmune reaction that destroys those cells leading to narcolepsy.
So this suggests just having the allele but not having narcolepsy causes sleep issues as well. How or why would be an interesting question if this research is not just finding noise.
 
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So this suggests just having the allele but not having narcolepsy causes sleep issues as well. How or why would be an interesting question if this research is not just finding noise.
I've not yet been able to look into this, but I wonder if being heterozygous for some of these things contribute to illness wtihout resulting in the full bore.

For example I'm heteroZ for EDS7...I don't have EDS, it seems (using their criteria) but collagen is missing, fingerprints gone, other anatomy collapsing.

So I' ve had an impaired sleep pattern likely for decades.
 

Alvin2

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I've not yet been able to look into this, but I wonder if being heterozygous for some of these things contribute to illness wtihout resulting in the full bore.

For example I'm heteroZ for EDS7...I don't have EDS, it seems (using their criteria) but collagen is missing, fingerprints gone, other anatomy collapsing.

So I' ve had an impaired sleep pattern likely for decades.
Its possible but its easy to rush to an easy explanation.
 

pattismith

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This is an incongruous result as narcolepsy is believed to be caused by destruction of orexin producing cells. If those cells are intact then you don't have narcolepsy. And presumably this allele increases the likelihood of the autoimmune reaction that destroys those cells leading to narcolepsy.
.
I agree this is not something I was especially looking for. I now have the SFN diagnosis, so I thought it may explain my whole disease.

But some months ago, my condition went worse after a flu vaccine.

-worse polyenthesopathy
-drop in my white cells/transitory neutropenia
-worse fatigue/sleepiness and pain

Corticosteroid or Piroxicam are able to help me, but my kidneys can no longer tolerate it, so I had to find something else.
I took narcolepsy drugs as a trial (methylphenidate/modafinil), and it fixed most of my ME/CFS/Fibro symptoms.( I don't know how it will do on the long run, though.)

-sleepiness
-headache
-exercice intolerance
-restless legs
-widespread pain

Then I sent my blood to the lab to check narcolepsy genes HLA DQB1*0602 and HLA DRB1*15 and I am a carrier for both.

Some other genes are involved in Narcolepsy or Hypersomnia that I was able to check on my 23andme datas and I am also carrier for the risk allele.

-rs1154155 TCA TCRA gene C/C = I have 2.5x risk for narcolepsy and a japanese study found a risk for Hypersomnia for this allele for people carying the haplotype HLA DQB1*0602 - HLA DRB1*15

-rs1551570 PPAN/P2Y11 gene C/T a chinese study found NT1 association
-rs2305795 P2Y11 gene A/G x 1.28 risk for narcolepsy

(you can also browse rs62360233, available on 23andme major allele C)
 

Alvin2

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I agree this is not something I was especially looking for. I now have the SFN diagnosis, so I thought it may explain my whole disease.

But some months ago, my condition went worse after a flu vaccine.

-worse polyenthesopathy
-drop in my white cells/transitory neutropenia
-worse fatigue/sleepiness and pain

Corticosteroid or Piroxicam are able to help me, but my kidneys can no longer tolerate it, so I had to find something else.
I took narcolepsy drugs as a trial (methylphenidate/modafinil), and it fixed most of my ME/CFS/Fibro symptoms.( I don't know how it will do on the long run, though.)

-sleepiness
-headache
-exercice intolerance
-restless legs
-widespread pain

Then I sent my blood to the lab to check narcolepsy genes HLA DQB1*0602 and HLA DRB1*15 and I am a carrier for both.

Some other genes are involved in Narcolepsy or Hypersomnia that I was able to check on my 23andme datas and I am also carrier for the risk allele.

-rs1154155 TCA TCRA gene C/C = I have 2.5x risk for narcolepsy and a japanese study found a risk for Hypersomnia for this allele for people carying the haplotype HLA DQB1*0602 - HLA DRB1*15

-rs1551570 PPAN/P2Y11 gene C/T a chinese study found NT1 association
-rs2305795 P2RY11 gene A/G x 1.28 risk for narcolepsy

(you can also browse rs62360233, available on 23andme major allele C)
If you have narcolepsy then i would suggest finding a narcolepsy doctor and being diagnosed because it can get very nasty without the right drugs.
 

pattismith

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@Alvin2
I fell aslept 4 times in my life in inappropriate situations (2 times while driving, one time in a classroom, one time in a theatre) when I had some sleep loss when I was young, so I am intolerant to sleep deprivation but I am not narco.

I had polysomnography years ago (maybe 10 years ago) and they found nothing.
 

Alvin2

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@Alvin2
I fell aslept 4 times in my life in inappropriate situations (2 times while driving, one time in a classroom, one time in a theatre) when I had some sleep loss when I was young, so I am intolerant to sleep deprivation but I am not narco.

I had polysomnography years ago (maybe 10 years ago) and they found nothing.
That doesn't sound like narcolepsy, though falling asleep twice while driving is very scary.
 

pattismith

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This is an incongruous result as narcolepsy is believed to be caused by destruction of orexin producing cells. If those cells are intact then you don't have narcolepsy. And presumably this allele increases the likelihood of the autoimmune reaction that destroys those cells leading to narcolepsy.
So this suggests just having the allele but not having narcolepsy causes sleep issues as well. How or why would be an interesting question if this research is not just finding noise.
Your definition of narcolepsy is restricted to Narcolepsy Type 1....but another is describe: NT2 with normal hypocretin/orexin level and zero cataplexy, but still with HLA DQB1*0602 association (but not so strong)
 

Alvin2

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Your definition of narcolepsy is restricted to Narcolepsy Type 1....but another is describe: NT2 with normal hypocretin/orexin level and zero cataplexy, but still with HLA DQB1*0602 association (but not so strong)
Type two means no muscle control loss, but falling asleep unexpectedly still occurs
 

pattismith

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Another study about the importance of HLA DQB1 0602 in excessive daily sleepiness (Parkinson cohort without narcolepsy)

Narcolepsy genetic marker HLA DQB1*06:02 and excessive daytime sleepiness in Parkinson disease patients treated with dopaminergic agents | SpringerLink 2022

Conclusion
PD individuals are more likely to experience EDS and fall asleep inappropriately during activities if DQB1*0602 positive. Genetic vulnerability may explain EDS risk in PD.
 
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now reminded I never figured this out....

I'm to f-ing exhausted to look for my DNA report, let alone look AT the DNA report.

One of my hugest issues is: cannot find anything, seem unable to organize anything and the mere act of thinking I should organize something is ...PEM inducing.