New Research Brings Clear Differences to Light in ME/CFS
by Suzanne D. Vernon, PhD | BHC Research Liaison
There is a great song in the musical RENT titled “Seasons of Love” in which they sing about the number of minutes in a year. As I am reviewing and writing this summary of the recent paper, “Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)”, I can’t help but sing it…
“Five hundred twenty-five thousand six hundred minutes
Five hundred twenty-five thousand moments so dear
Five hundred twenty-five thousand six hundred minutes
How do you measure, measure a year?
This song has impact. Maybe because it’s a big number, or because it’s precise, or because we don’t normally think of a year in minutes. Whatever the reason, it is an enduring anthem that I have stuck in my head. Here’s my rendition related to this research…
“Twelve thousand six hundred and eight methylated sites
Twelve thousand six hundred and eight differences oh dear
Twelve thousand six hundred and eight methylated sites
How do you measure, differences so clear?”
That’s right … 12,608 differences on the DNA between ME/CFS patients compared to matched healthy people. That’s a big biological difference. That’s what Wilfred de Vega, a PhD student in Dr. Patrick McGowan’s laboratory, detected in a paper published in the open access journal BMC Medical Genomics titled, “Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)”. These differences on the DNA also affect immune cell function.
You can read the paper HERE, but let me break down this important research.
“Epi” means above and epigenetics implies “above the DNA” of our genes. These are the chemical changes that occur to our DNA – such as the addition of sticky methyl groups – that change how our genes are expressed. In other words, the function of the gene is changed without changing the underlying DNA sequence. Lots of methylation can silence gene expression and no methylation means gene expression is turned on. This team found that almost half of the 12,608 methylation sites were located in protein coding genes. There was more hypermethylation of the DNA in ME/CFS patients (71.6% versus 28.4% hypomethylated) compared to controls. A full 1,600 differentially methylated genes were associated with physical impairment in ME/CFS. Notably many of these genes are involved in cell energy production, metabolism and immune signaling.
de Vega tested to see whether these differences could affect immune function. He took blood cells from ME/CFS patients and healthy controls and used a specific assay to activate the immune cells (to simulate an immune response) and then turn off the response using a synthetic cortisol. (Remember, cortisol calms the immune response). The blood cells from a subgroup of ME/CFS patients were hypersensitive to the cortisol meaning that the amount needed to calm healthy immune cells caused the ME/CFS immune cells to shut down. There were 13 differentially methylated genes associated with this hypersensitivity to cortisol in the ME/CFS subgroup.
These are big numbers of differences precisely mapped to genes in ME/CFS patients that clearly affect immune cell function and physical function. We don’t yet know is what causes these epigenetic differences. Innovative research being conducted by young investigators like Dr. Patrick McGowan and his team puts us hot on the trail to track that down.
If anyone still doubts the biological basis of ME/CFS, I would ask them to read this paper, then ask… How could it be more clear?