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. 2005 Mar 24;5(1):5.
doi: 10.1186/1472-6793-5-5.

Exercise responsive genes measured in peripheral blood of women with chronic fatigue syndrome and matched control subjects

Toni Whistler  1 , James F Jones, Elizabeth R Unger, Suzanne D Vernon
Affiliations

Exercise responsive genes measured in peripheral blood of women with chronic fatigue syndrome and matched control subjects

Toni Whistler et al. BMC Physiol. .

Abstract

Background: Chronic fatigue syndrome (CFS) is defined by debilitating fatigue that is exacerbated by physical or mental exertion. To search for markers of CFS-associated post-exertional fatigue, we measured peripheral blood gene expression profiles of women with CFS and matched controls before and after exercise challenge.

Results: Women with CFS and healthy, age-matched, sedentary controls were exercised on a stationary bicycle at 70% of their predicted maximum workload. Blood was obtained before and after the challenge, total RNA was extracted from mononuclear cells, and signal intensity of the labeled cDNA hybridized to a 3800-gene oligonucleotide microarray was measured. We identified differences in gene expression among and between subject groups before and after exercise challenge and evaluated differences in terms of Gene Ontology categories. Exercise-responsive genes differed between CFS patients and controls. These were in genes classified in chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport, and G protein-coupled receptor ontologies. Differences in ion transport and ion channel activity were evident at baseline and were exaggerated after exercise, as evidenced by greater numbers of differentially expressed genes in these molecular functions.

Conclusion: These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS.

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Figures

Figure 1
Figure 1
Hierarchical clustering of exercise responsive genes in control subjects. The 21 differentially expressed genes identified by a class comparison test of control subjects (before and after exercise challenge (Table 2)) were clustered using a two-way hierarchical algorithm. In the matrix each row represents the hybridization results for a single gene, and each column represents a subject. Transcript levels are depicted as above (red) or below (green) the mean. The dendograms illustrates average-linkage hierarchical clustering of subjects (top) and genes (left). Refseq IDs for each gene is given on the right of the matrix. Those with similar exercise responses in both CFS and control subjects are at the top of the matrix, and the remainder of genes (highlighted in blue) show a diminished exercise response in CFS cases. Refseq IDs highlighted in yellow classify to the GO categories of protein or vesicle-mediated transport (Biological Process). Refseq IDs followed by: formula image are classified to the GO category of binding (Molecular Function); and/or # are classified in the GO category of metabolism (Biological Process). The subjects group into 4 clusters which approximate to: 1) Control subjects before exercise (Con0); 2) CFS cases before exercise (CFS0); 3) Control subjects after exercise (Con24); and 4) CFS cases after exercise (CFS24).
Figure 2
Figure 2
Significant gene ontology categories defining exercise-related changes in control (a) and CFS subjects (b). The three organizing principles of GO (represented as grey shaded boxes) are molecular function, biological process, and cellular component. Related ontologies and/or subgroups of the ontologies are denoted by similarly colored squares in all tables. Ontologies presented in these figures were significant at a p-value <0.005 by one or both of the LS and KS permutation tests.
Figure 3
Figure 3
Gene Ontology categories identified as significantly different between controls and CFS cases at baseline (pre-exercise) (a) and post-exercise (b). The three organizing principles of GO (represented by grey shaded squares) are molecular function, biological process, and cellular component. Related ontologies and/or subgroups of the ontologies are denoted by similarly colored squares in all tables. Ontologies presented in these figures were significant at a p-value <0.005 by one or both of the LS and KS permutation tests.
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