. Author manuscript; available in PMC: 2014 Oct 16.

Published in final edited form as: Qual Life Res. 2014 Mar 7;23(7):1997–2013. doi: 10.1007/s11136-014-0656-1

Table 1.

Biological Pathways, Candidate Genes and Molecular Markers in Fatigue

Quality of Life Domains	Biological Pathways^*	Candidate genes	Biomolecular markers	Literature

*Fatigue*				• (1)

	• Serotonergic synapse/metabolic pathway	• TPH1	• 5-HT	• (2–5)

	• Dopaminergic synapse	• COMT, DRD4, DAT1	• Cortisol	• (6, 7)

	• Glutathione metabolic pathway	• GSTZ1, ABCC4, DPYD, GSTP1, OPRT/UMPS	-NR-	• (8–10)

• Inflammation	• Cytokine-cytokine receptor interaction			• (11)
	◆ pro-inflammatory	• IL-1β, IL-6, TNF-α, CD19+β	• IL-1β, IL-6, TNF-α, CD19+β, TNF-R1,	• (12–25)
	◆ anti-inflammatory	• IL-1RN, IL-1Rα, IL-10	• IL-1RN, IL-1Rα, IL-10	• (13–15, 17)
	◆ immunity	• IL-2, IL-4, IL-5, IFN-γ	• IL-2, IL-4, IL-5, IFN-γ	• (12, 26)
	◆ cell migration	• CXCL9, CXCL11	• CXCL9, CXCL11	• (27)
	◆ inflammation	• CRP	• CRP, neopterin	• (4, 13)

• Cortisol production, serotonin dysregulation, catecholamine	• HPA	-NR-	• CRH, ACTH, cortisol, melatonin, norepinephrine, epinephrine	• (28–31)

• Circadian rhythm disruption – i.e. through modulation of arousal and sleep patterns	• SCN	• PER2, PER3, TIMELESS	• EGF, TGF-α, neuregulin-1, prokineticine-2, cardiotrophin-like cytokine, PER2, PER3, cortisol, melatonin	• (28, 32–37)

	• EGFR	-NR-	-NR-	• (28)

• Peripheral fatigue (muscle strength)	• Skeletal muscle	-NR-	• ATP	• (37, 38)

• Vagal afferent nerve activation (suppress somatic muscle activity – ‘sickness behavior’)	• Cytokine-cytokine receptor interaction
	◆ pro-inflammatory	• IL-1, IL-6, TNF-α	• IL-1, IL-6, TNF-α	• (39)

Biological pathways are according to KEGG (Kyoto Encyclopaedia of Genes and Genomes), http://www.genome.jp/kegg/ or Genecards, http://www.genecards.org/

Note: References are included in Supplementary Material 2: References to Tables 1–7.

NR: the relevant information was not reported

?: the relevant biological pathway could not be identified