Article Index

Genomics and genetics

Expression patterns of genes relevant to immune function were discussed by E. Brenu (Gold Coast, Australia). Her study confirmed changes in microRNA expression in cytotoxic cells that may be related to the poor function of these cells in CFS patients.

M.Rajeevan (Atlanta, USA) had looked at the immune and inflammatory alterations in CFS to determine if genetic variants in inflammation and immune pathways could be linked to CFS, as well as to quantitative measures of functional impairment, fatigue and symptom inventory. Compared to controls, CFS was associated with 34 functionally relevant single nucleotide polymorphisms (SNPs). 12 of these are in pathways related to complement cascade, chemokines and cytokines/cytokine signalling and Toll-like receptor signalling. Differences in these associations found for subjects with exclusionary conditions otherwise meeting criteria for CFS, suggests important differences between these groups.

L.Bateman (Salt Lake City, USA) presented work to determine whether baseline and/or post-exercise expression of genes involved in signalling and modulating sensory fatigue and muscle pain are potential biomarkers for distinguishing those with CFS and FM from healthy controls. At least 2 sub-groups of patients were identified by gene expression following exercise. The larger subgroup showed increases in mRNA for sensory ion channels and adrenergic receptors and a cytokine. Symptom severity was associated with greater post-exercise increases in these genes. The smaller subgroup were mainly patients with orthostatic intolerance and there was no post-exercise increase in any gene, and was defined by decreases in mRNA for α2A adrenergic receptor. The FM only patients were identified by baseline increases in 3 genes. Post-exercise increase in 4 genes distinguished CFS from controls, and could be an objective biomarker for CFS. Diagnosis based on gene expression may eventually be possible.

Following work with Gulf War veterans, L.Steele (Waco, USA) investigated, with a small sample whether exposure to neurotoxicants are risk factors for developing Gulf War Illness (GWI). Some troops who were exposed however did not develop illness, so genetic differences may have been implicated.  Findings are supportive that GWI may be associated with the PON1 genotype. PON1 is a detoxifying enzyme. GW veterans whose PON1 genotype is known to provide slower hydrolysis of some organophosphate pesticides are at greater risk of GWI in relation to reported use of pesticides and prolonged use of pyridostigmine. And GW veterans who carry the R allele PON1192, which is known to provide inefficient hydrolysis of sarin were at increased risk of GWI if they had heard chemical alarms, which indicated potential exposure.

L.Garcia (Miami, USA) compared gene expression patterns in CFS and GWI. Study was based on Jonathan Kerr’s work which had identified 79 genes associated with CFS with defined subgroups. Her group used gene activation patterns in CFS and GWI during and after exercise challenge to better understand the mediators of persistence and relapse. Kerr’s earlier findings were confirmed in the CFS group. There were significant differences when compared to controls. There were important overlaps with GWI. EB12 (an EBV induced gene) was 6-fold higher in CFS than in controls, and 2-fold higher in GWI. ETS1 was upregulated in both groups. Transcription factor 3 was markedly elevated in GWI and less so in CFS, though was significant. Apoptosis genes were markedly elevated in both groups though 400 fold higher in GWI. The overall trend however was that most of the gene regulation activities associated with CFS were not significantly different between GWI and controls. Additional genes specific to GWI have however been identified by the group. With exercise challenge, there were changes in genes at peak of exercise which were unique to CFS. This was accompanied by altered immune signalling pathways.