Dynamic epigenetic changes during a relapse and recovery cycle in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome
Epigenetics is the study of how your behaviors and environment can cause changes that affect the way your genes work. Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence. (CDC)
A New Zealand research team led by Prof Warren Tate explored changes in the genes of 2 patients with ME/CFS during a relapse which resulted in “functionally important changes in their DNA methylomes that, while differing between the two patients, led to very similar compromised physiology.
Conclusions
This study shows the benefits of precision medicine for individual patients with a disease as physiologically complex as ME/CFS.
Precision medicine – an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. (NLH)
Currently, ME/CFS patients can respond quite differently to specific medications, for example supplements like vitamin B12, and to anti-inflammatory drugs like naltrexone, and to physiological states like pregnancy, with some showing marked improvement, some marked deterioration, and some seemingly no change in their condition.
By considering individual patients over the course of their ME/CFS disease we can better understand not only the similarities within the overall patient group, but also develop an in depth understanding of the fluctuations for each patient that relates to their specific pathophysiology.
Variable methylation of regulatory regions associated with the relapse condition has in this study identified a number of genes with key functional roles in immune, inflammatory, metabolic and mitochondrial pathways.
For a disease that has proven challenging to diagnose and characterise, with the delay in diagnosis detrimental for the affected person, this kind of analysis provides not only further evidence of serious biological dysfunction, but importantly also ongoing systematic molecular changes that inform future targets for individual treatment or symptom management as we continue to unravel and understand the complex nature of ME/CFS.
Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, by Amber M Helliwell, Peter A Stockwell, Christina D Edgar, Aniruddha Chatterjee, Warren P Tate in Int J Mol Sci. 2022 Oct 6;23(19):11852 [doi: 10.3390/ijms231911852]
Research abstract:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease with variable severity. Patients experience frequent relapses where symptoms increase in severity, leaving them with a marked reduction in quality of life.
Previous work has investigated molecular differences between ME/CFS patients and healthy controls, but not the dynamic changes specific to each individual patient. We applied precision medicine here to map genomic changes in two selected ME/CFS patients through a period that contained a relapse recovery cycle.
Method
DNA was isolated from two patients and a healthy age/gender matched control at regular intervals and captured the patient relapse in each case. Reduced representation DNA methylation sequencing profiles were obtained spanning the relapse recovery cycle. Both patients showed a significantly larger methylome variability (10-20-fold) through the period of sampling compared with the control.
Results
During the relapse, changes in the methylome profiles of the two patients were detected in regulatory-active regions of the genome that were associated, respectively, with 157 and 127 downstream genes, indicating disturbed metabolic, immune and inflammatory functions.
Severe health relapses in the ME/CFS patients resulted in functionally important changes in their DNA methylomes that, while differing between the two patients, led to very similar compromised physiology.
DNA methylation as a signature of disease variability in ongoing ME/CFS may have practical applications for strategies to decrease relapse frequency.
