Gene Expression Correlates of Unexplained Fatigue

Abstract

Chronic Fatigue Syndrome (CFS) is a debilitating illness and as unexplained fatigue is a central feature of the case definition, we sought to determine peripheral blood gene expression correlates of fatigue using Quantitative Trait Analysis. Women identified in a population based survey of Wichita residents with CFS (n=39), other fatiguing illnesses (n=35) and non-fatigued controls (n=37) were studied. MWG oligonucleotide arrays were hybridized with biotinylated cDNA and detected with Resonance Light Scattering. Background-subtracted intensities were quantile normalized and genes that did not vary more than replicates were omitted. The 15,300 genes were correlated with fatigue measures from the Multidimensional Fatigue Inventory. The Spearman coefficient identified 839 genes, 50% mapping to metabolic and cell regulatory pathways. Nine genes, including proteins in the ATP binding cassette family, transcription initiation factor complex, mitochondrial ribosome, and programmed cell death, were reported independently validated in association with CFS [JPath(2005)58:826]. The metabolic pathways affected indicate impaired energy metabolism as a result or cause of mitochondrial dysfunction and cell regulatory pathways include the mTOR, Jak-STAT and MAPK signaling.