Abnormal gene profile found in chronic fatigue patients

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Abnormal gene profile found in chronic fatigue patients

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August 12, 2005

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Janis

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London, UK - Patients with chronic fatigue syndrome (CFS) have

abnormalities in gene expression, and these changes carry intriguing

hints about factors that might trigger or contribute to this syndrome,

according to Dr R Kerr (now at St 's University of

London, UK). Kerr and colleagues at Imperial College, London, report in

two papers in the August 2005 issue of the Journal of Clinical

Pathology that they have identified a reproducible gene-expression

profile in peripheral blood monocytes from CFS patients [1] and that

CFS may be associated with the HLA-DQA1*01 allele [2].

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" The fact that we have found reproducible changes in gene function in

CFS supports the view that this disease has a biological or organic

basis, and is not just in the mind. "

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" Historically, CFS has been relatively unexplained in terms of

biological function. This pilot study was designed to test the

hypothesis that abnormalities of gene regulation occur in CFS, and we

have shown that to be the case, " Kerr tells rheumawire. " We have now

taken this a step further and identified the very pathways involved,

and that will be described in our next paper. The fact that we have

found reproducible changes in gene function in CFS supports the view

that this disease has a biological or organic basis and is not just in

the mind. "

Genes suggest T-cell, neuron, and mitochondrial changes

In the first paper, the researchers describe a characteristic

gene-expression profile in CFS patients, which includes upregulation of

15 genes and downregulation of one gene compared with normal controls.

They also note that the specific genes involved suggest T-cell

activation, neuronal abnormalities, and mitochondrial-function

abnormalities.

This study was done using peripheral blood mononuclear cells from 25

patients with CFS diagnosed according to the Centers for Disease

Control criteria and 25 normal blood donors matched for age, sex, and

geographical location. The analysis used a single color microarray

representing 9522 human genes, and genes showing differential

expression were further analyzed using TaqMan real-time polymerase

chain reaction in fresh samples.

Among the genes upregulated were those for neuropathy target esterase

(NTE) and eukaryotic translation initiation factor 4G1 (EIF4G1). " These

genes are the targets for organophosphates and viruses, respectively, "

Kerr says. " Therefore, we hypothesize that upregulation of each may

reflect a host response to an insult, which attempts to overcompensate

in each case. "

The upregulated genes could be grouped according to immune, neuronal,

mitochondrial, and other functions relevant to CFS. The gene-expression

profile suggested T-cell activation, upregulation of protein kinase C

family members implicated in various psychiatric and affective

disorders, abnormalities of microtubule proteins in neurons, and

changes in several aspects of mitochondrial function.

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" This group is about to begin clinical trials using experimental drugs

chosen on the basis of the CSF gene-expression findings. "

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http://www.jointandbone.org/viewArticle.do?primaryKey=541947