Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome

Abstract

Objectives To determine mRNA expression differences in genes involved in signaling and modulating sensory fatigue, and muscle pain in patients with Chronic Fatigue Syndrome (CFS) and Fibromyalgia Syndrome (FM) at baseline, and following moderate exercise. Design Forty eight Patients with CFS-only, or CFS with comorbid FM, 18 Patients with FM that did not meet criteria for CFS, and 49 healthy Controls underwent moderate exercise (25 minutes at 70% maximum age predicted heart-rate). Visual-analogue measures of fatigue and pain were taken before, during, and after exercise. Blood samples were taken before, and 0.5, 8, 24, and 48 hours after exercise. Leukocytes were immediately isolated from blood, number coded for blind processing and analyses, and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic, and immune functions was compared between groups at baseline, and following exercise. Changes in amounts of mRNA were correlated with behavioral measures, and functional clinical assessments. Results No gene expression changes occurred following exercise in Controls. In 71% of CFS patients, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 hours. These post-exercise increases correlated with behavioral measures of fatigue and pain. In contrast, for the other 29% of CFS patients, adrenergic α-2A receptor’s transcription was decreased at all time points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM only patients showed no post-exercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than Controls. Conclusions At least two subgroups of CFS patients can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the CFS patients with orthostatic intolerance, showed no post-exercise increases in any gene, and was defined by decreases in mRNA for α-2A. FM only patients can be identified by baseline increases in 3 genes. Post-exercise increases for 4 genes meet published criteria as an objective biomarker for CFS, and could be useful in guiding treatment selection for different subgroups.

Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome

“…These findings contrast with those of previous studies 35,36 in which similar dosages and plasma concentrations of clonidine had a significant and dosedependent effect on blood pressure and heart rate. A potential plasma-expanding effect of clonidine might offset blood 48 of abnormal α 2 -receptor protein transcription in CFS. Alteration of pharmacodynamics might also explain the association between high clonidine concentration and insomnia problems in the present study despite the well-known sedative effect of clonidine and the lack of clonidine's effect on working memory.…”

Hva er egentlig myalgisk encefalopati?

“…Hormonelle forstyrrelser er påvist, spesielt for stressfysiologiske mekanismer som involverer HPA-aksen (hypothalamus -hypofyse -binyrebark-aksen) (33,34) . Undersøkelser av pasienter med CFS/ME før og etter fysisk anstrengelse, kan tyde på at de har en endret genregulering etter belastning i forhold til friske (35,36) .…”

149. Epigenetic Alterations and an Increased Frequency of Micronuclei in Women With Fibromyalgia

“…Despite showing a strong familial aggregation [8][9][10], attempts to identify genetic factors associated with FM (primarily through polymorphism 2 Nursing Research and Practice association studies) have yielded inconsistent results, with some investigators showing associations between FM and specific genes (including, but not limited to, genes for catechol-O-methyltransferase [11][12][13], serotonin-2A receptor [14,15], serotonin transporter gene regulatory region [16,17], dopamine D4 receptor [18], -2 adrenergic receptor [19], gamma-aminobutyric acid receptor subunit beta-3, trace amine-associated receptor 1, interferon-induced guanylatebinding protein 1, regulator of G protein signaling 4, cannabinoid receptor type 1, and glutamate receptor 4 [20]), while others failed to identify a relationship [21][22][23][24][25]. Since a consistent, straightforward association with a gene (s) has not yet been forthcoming, scientists have suggested that the familial influence on FM may more likely reflect a genetic susceptibility to environmental events [21,26,27]. For example, Klengel and Binder [28] identified differential methylation for a glucocorticoid response element (the FKBP5 gene) that resulted from the presence of both an "at-risk" allele (polymorphism) and the occurrence of childhood trauma in subjects they studied who had posttraumatic stress disorder.…”