Search for Gene-Altering Triggers in Chronic Fatigue Syndrome Heats Up at U Toronto

 Epigenetics is the study of changes in a gene’s ‘expression’ – and of the factors that trigger those changes. University of Toronto epigeneticist Patrick O McGowan, PhD, is actively studying the epigenetics of chronic fatigue syndrome – whether, when, how, to what extent, and in what circumstances the expression of certain genes may determine susceptibility to or drive ME/CFS.

Specifically, Dr. McGowan is examining how environmental triggers might alter gene expression so as to alter immune function and stress response in ways that contribute to ME/CFS.

• Epigenetic changes in gene function don’t change the gene itself – the underlying DNA sequence.

• They’re more a case of possible activities being turned on or turned off.

• Epigenetic changes can be caused by environmental triggers, which can include factors such as infections, toxins, stress, nutrition, and even the social environment.

• The question being, how much of the patient’s gene expression is explained by inherited DNA, and how much by effects of the environment?

Dr. McGowan will conduct his study of the epigenetics of ME/CFS with a grant from the CFIDS Association of America. As part of the grant, he will have access to the SolveCFS Biobank, a collection of biological samples from ME/CFS patients.

Looking for Clues in Banked ME/CFS Blood & Tissue Samples

Specifically, Dr. McGowan will look at the relationship between a system called the hypothalamic-pituitary-adrenal (HPA) axis and immune function.

The HPA axis is involved in the regulation of the stress response, and has effects on immune activity and inflammation through cellular signaling mechanisms involving the steroid glucocorticoid.

Glucocorticoid (cortisol is a glucocorticoid) in fact has a “huge number” of physiological influences, including glucose concentration in the blood, cognitive function, and sleep cycles. Essentially every cell in the body has glucocorticoid receptors. 

Dr. McGowan’s hypothesis is that there is an epigenetic mechanism in CFS that disrupts glucocorticoid signaling in white blood cells called lymphocytes, which are responsible for immune responses.

By studying tissue samples from the SolveCFS Biobank he hopes to pinpoint the mechanism. This repository of tissue and blood samples is part of the Genetic Alliance Registry and BioBank.

Dr. McGowan’s previous investigations have involved for example the effects on epigenetic expression of inadequate methyl-related nutrients in the diet (e.g., folate, methionine, B12 and B6), fetal nutritional restriction, maternal behavior, social adversity, and fear/abuse-related stress.

ME/CFS, or “CFIDS” (Chronic Fatigue and Immune Dysfunction Syndrome) is a complex and debilitating chronic illness that affects the brain and multiple body systems. Symptoms include incapacitating fatigue and problems with concentration and short-term memory. Millions of North Americans are thought to suffer from the disease.

Source: Based on University of Toronto, Scarborough news release, Feb 23, 2012

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