Genomics Day 2005: Genomics Day 2005: Public Health Genomics at CDC
Group 2: Biomarker Discovery
Exercise induced exacerbation of symptoms associated with chronic fatigue syndrome to identify differentially expressed fatigue genes
Whistler T, Vernon SD , Clancy K, Jones JF, Reeves WC.
Division of Viral and Rickettsial Diseases, NCID, CDC
Chronic Fatigue Syndrome (CFS) presently has no diagnostic clinical signs or laboratory abnormalities and is defined solely by symptoms. This syndrome is characterized by persistent or relapsing debilitating mental and physical fatigue that is exacerbated by minor exertion. This generally produces an increase in the severity of the range of symptoms typically experienced by patients with CFS. This study was designed to utilize this phenomenon in an attempt to acquire an understanding of the underlying biologic correlates of CFS.Patients with CFS and age-matched, normal control subjects were exercised on a stationary bicycle at 70% of their predicted maximum workload. Blood samples were taken before and after the exercise challenge. Total RNA was extracted from peripheral blood mononuclear cells and hybridized to a 3800-gene oligonucleotide microarray.
Data analysis involved looking for differentially expressed genes between subjects grouped by the following criteria:
- Cases or controls,
- Pre or post exertion,
- Cases: pre exercise time point versus cases: post exercise,
- This same analysis (3) performed on the control subjects.
Differentially expressed genes in controls pre and post exercise were related to energy metabolism, muscle and immune response (T-cell associated chemokines and receptors). Cluster analysis on genes differentially expressed at 24h post exertion was used to identify genes that may predict caseness. Several of these genes were involved in transcriptional regulation, metabolism and the immune response. These same genes could also classify case from control prior to exercise.
The molecular and biological functions of these genes were mapped by data mining allowing for associations to be made between the differing gene lists. We put forward some mechanisms possibly associated with exacerbation of CFS symptoms and the possible differences in how CFS subjects cope with stress compared to controls. These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS.