Gulf war illness: a tale of two genomes 2024 Golomb et al

[Andy]

Abstract

Introduction
Gulf War illness (GWI) is an environmentally-triggered chronic multisymptom illness typified by protean symptoms, in which mitochondrial impairment is evident. It has been likened to accelerated aging. Nuclear genetics of detoxification have been linked to GWI.

Objective
To see whether mitochondrial (mt) haplogroup U – a heritable profile of mitochondrial DNA that has been tied to aging-related conditions – significantly predicts greater GWI severity; and to assess whether GWI severity is influenced by mitochondrial as well as nuclear genetics. 54 consenting Gulf War veterans gave information on GWI severity, of whom 52 had nuclear DNA assessment; and 45 had both nuclear and mitochondrial DNA assessments. Regression with robust standard errors assessed prediction of GWI severity as a function of nuclear genetics (butyrylcholinesterase variants), mitochondrial genetics (haplogroup U, previously tied to aging-related conditions); or both.

Results
BChE “adverse” variants significantly predicted GWI severity (β(SE) = 23.4(11.4), p = 0.046), as did mt haplogroup U (β(SE) = 36.4(13.6), p = 0.010). In a model including both, BChE was no longer significant, but mt haplogroup U retained significance (β(SE) = 36.7(13.0), p = 0.007). This is the first study to show that mitochondrial genetics are tied to GWI severity in Gulf-deployed veterans. Other data affirm a tie to nuclear genetics, making GWI indeed a “tale of two genomes.”

Open access, https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-024-06871-z

 

[Amw66]

I don't know if Decode ME scope includes these genes - it would be interesting to see if there's any similarity .


" Gulf War illness (GWI), a chronic fatigue condition affecting veterans, is linked to genetic variants in mitochondrial DNA. These variants, inherited through the maternal line, appear to predispose some individuals to more severe symptoms of GWI after exposure to environmental toxins.

The study suggests that mitochondrial dysfunction, rather than inflammation, is the primary driver of the illness. These findings may also have broader implications for understanding other diseases with environmental triggers, such as Parkinson’s disease."

https://neurosciencenews.com/mitochondrial-dna-gulf-war-illness-27702/

Paper
https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-024-06871-z

 

[forestglip]

Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome, 2016, Billing-Ross et al

The subjects were diagnosed by physicians expert in ME/CFS and met either the Fukuda criteria [24] and/or the canadian consensus criteria [25] for diagnosis.

No ME/CFS subject exhibited known disease-causing mtDNA mutations. Extent of heteroplasmy was low in all subjects. Although no association between mtDNA SNPs and ME/CFS vs. healthy status was observed, haplogroups J, U and H as well as eight SNPs in ME/CFS cases were significantly associated with individual symptoms, symptom clusters, or symptom severity.

individuals belonging to haplogroup U reported less severe bloating and had lower bloating distress scores compared to other haplogroups.

 

[forestglip]

MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants, 2019, Venter et al

Both cohorts met the Fukuda diagnostic criteria

Thus as in the work of Billing-Ross et al. [prior post], mtDNA haplogroup [including U] was not seen to affect the susceptibility to ME/CFS

 

[forestglip]

BChE being discussed in the recent Ponting paper thread:

It looks like the protein with the greatest significance for men only is BCHE (adjusted p=0.0003) which is a cholinesterase - Butyrylcholinesterase.



Its function appears to be as a non specific cholinesterase that is structurally similar to acetylcholinesterase, but that in addition to just acetylcholine it also breaks other chain lengths acylcholines as well as certain drugs. It's produced in the liver and it's blood levels can be indicative of liver function supposedly.

Its cohen's d effect size from the raw data is 0.8, and its Total Effect is also significant in the paper. I'd be curious to see what the raw data looks like as a strip scatter plot. With cohen's d=0.8, normal distributions, and the sample sizes used here I guess it might look something like this simulation I made: