Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: The al-Ándalus project, 2021, Estévez-López et al

Abstract

Objectives
It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA) and that pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate-genes) and the gene-gene, gene-PA, and gene-sedentary behaviour interactions with pain and pain-related cognitions in women with fibromyalgia.

Methods
Saliva samples from 274 women with fibromyalgia (aged 51.7 ± 7.7 years) were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed.

Results
The rs6311 and rs6313 polymorphisms (HTR2A) were individually related to algometer scores. The interaction of rs4818 (COMT) and rs1799971 (OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (ADR1A), rs6860 (CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the SF-36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of fibromyalgia symptoms (codominant model, p-value: 0.032).

Conclusion
The HTR2A gene (individually), COMT and OPRM1 gene-gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT, and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene-sedentary behaviour interaction to pain and pain catastrophizing in women with fibromyalgia. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.

Open access, https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab911/6454963

 

As always my heart sinks with lines like “It is widely acknowledged that … … …”, and these are the opening words of this abstract.

 

When I was at university, our lecturers told us that if we used the phrase "everyone knows" (or similar) in an essay, it would receive an automatic fail.

Doctors and their Royal Colleges love to boast about their high educational standards, but this really seems to be nothing but hot air.

 

My rheumatologist back in 1996 told me "use heat, heat, heat" for my newly diagnosed FM.

True today. Lie or sit back on heating pad to upper body parts. Sorry, researchers, but that's sedentary. Hmm, maybe a balance of careful movement and heat-sedentary "behaviors" would yield a more robust gene picture for your research?

Or, you could just ask people with FM what works for them. Novel idea.

And are the genes they chose to compare, are they highly validated to relate to changes in pain perception?

 

Assuming that the methodology is sound (no controls and a smallish sample might be a concern, but perhaps not relevant for this kind of study) then this looks not unreasonable. The Conclusion:

offers a falsifiable hypothesis - "activity increase in fibromyalgia sufferers with genetic susceptibility to pain is associated with reported decreases in pain experience, no such improvement is noted in fibromyalgia sufferers with no genetic susceptibility to pain". If that hypothesis survives then there would be a useful, and targettable addition to pain management in fibromyalgia. If the hypothesis doesn't hold up then research moves on to something else.

 

Another gene polymorphisms of COMT study, same ideas https://pubmed.ncbi.nlm.nih.gov/21130573/

 

Mmmm COMT has many functions and impacts many processes. Inflammation, detoxification , cardiovascular, energy production as well as neurotransmitter synthesis.... seratonin and estrogen have roles in pain mediation ( and cohort is female - so was time on menstrual cycle controlled for?).

I struggle with correlation posited as potential causation for complex systems where signalling feedback loops may not be understood.

To be applicable genes also have to be capable of functioning
Was cofactor status checked ?

 

The great advantage of DNA studies - studies of the gene pattern present from the earliest cell in your embryo at conception is that the DNA pattern must come first and so any correlation has to be causal. The only exception to this is I can think of are 1. if there is linkage disequilibrium, which means that you may not be sure which genes out of the pattern are doing the causing. 2. if there is some confounding social factor like poverty associated with race.

Feedback loops do not come in to this. DNA does not change with menstrual cycle or with gene usage or cofactor availability. RNA levels do, as in gene expression studies, but that is something else.

It is the 'interplay with lifestyle' that is where I would be sceptical about interpretation.

 

Thanks for the clarification - obviously I am confused and early morning is not my best time for sussing anything . It has been a long night!
Can you further enlighten me ?

When a gene multi tasks and does have more than 1 role , do we know fully what it is responding to -is this the RS aspect and/or one of expression.

The signalling feedback loops would be gene expression ?

To me ME is very like climate change science and whilst this has an uncanny accuracy within defined parameters there are always surprises when things don't behave as expected ( usually due to feedback reinforcement but also sometimes a lack of joined upness in the thought process)