How do alterations in the COMT gene affect inflammation in ME/CFS and fibromyalgia?

Principal investigator

Prof. Jo Nijs
Vrije Universiteit Brussel, Brussels, Belgium

About the study

The aim of this study was to understand better the disease processes underlying the development of ME/CFS and fibromyalgia.

The researchers were interested specifically in a protein called catechol-O-methyltransferase (COMT) which is known to have effects on pain and inflammation, both of which are key features in these diseases.

The instructions to build proteins are contained in our genes, but alterations to these genes can change how they behave, and consequently how the proteins function.

Very simply, a genetic alteration is a change to the DNA in a gene, while an epigenetic alteration is a change to how the gene behaves.

The researchers wanted to investigate a number of genetic and epigenetic alterations to the COMT gene in patients with ME/CFS and fibromyalgia, and whether they were associated with markers of inflammation or clinical symptoms.

Clinical information and blood samples were collected from 28 patients meeting diagnostic criteria for both ME/CFS and fibromyalgia, and from 26 healthy control subjects.

The blood samples were analysed to assess a number of factors:

  • Polymorphisms in the COMT gene (these are genetic alterations, or mutations),
  • DNA methylation in the COMT gene (this is an epigenetic alteration), and
  • Levels of several substances (cytokines) associated with inflammation.

The researchers found polymorphisms in the COMT gene in patients with ME/CFS and fibromyalgia, and also to a similar degree in healthy control subjects. The specific patterns of changes corresponded to the level of activity of the COMT protein.

However, the patient group had around twice the level of DNA methylation (the epigenetic alteration) as was seen in the control group.

The patients also had significantly lower levels of interferon gamma, which is a cytokine known to play a role in inflammation.

The researchers believe their findings may point to DNA methylation of the COMT gene as being an important factor in the development of ME/CFS and fibromyalgia.

Higher methylation levels might be associated with lower activity of the COMT protein and worse symptoms, although more research is needed to explore this more closely.

Epigenetics continues to be an exciting area within ME/CFS research, and you can read more about this field in Cort Johnson’s article Resetting ME/CFS with epigenetics?, which also highlights Prof. Nijs’s body of work.


Polli A, Hendrix J, Ickmans K, Bakusic J, Ghosh M, Monteyne D, Velkeniers B, Bekaert B, Nijs J, Godderis L. Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia. Journal of Translational Medicine, 2022 October 25; 20(1):487.

Supported by

ME Research UK
Research Foundation – Flanders

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