A predictive algorithm to identify genes that discriminate individuals with fibromyalgia syndrome

mariovitali

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@Murph something related to my confirmation bias ;-)


A predictive algorithm to identify genes that discriminate individuals with fibromyalgia syndrome diagnosis from healthy controls

A predictive algorithm to identify genes that discriminate individuals with fibromyalgia syndrome di
Objectives: Fibromyalgia syndrome (FMS) is a chronic and often debilitating condition that is characterized by persistent fatigue, pain, bowel abnormalities, and sleep disturbances. Currently, there are no definitive prognostic or diagnostic biomarkers for FMS. This study attempted to utilize a novel predictive algorithm to identify a group of genes whose differential expression discriminated individuals with FMS diagnosis from healthy controls.

Results: The small-scale signature contained 57 genes whose expressions were highly discriminatory of the FMS diagnosis. The combination of these high discriminatory genes with FR higher than 1.45 provided a leave-one-out-cross-validation accuracy for the FMS diagnosis of 85.11%. The discriminatory genes were associated with 3 canonical pathways: hepatic stellate cell activation, oxidative phosphorylation, and airway pathology related to COPD.


Interestingly, hepatic fibrosis is mentioned in the paper :






and to be fair :


Follow-up studies are warranted to address several limitations of the study. There is a very high likelihood that the list of genes generated in this study maybe artifacts of over training on a single cohort of a small number of patients. For the findings to have clinical and diagnostic utilities, the predictive genes must be validated in a larger, independent cohort of patients with FMS. Further, future studies should account the overlap of FMS and ME/CFS diagnoses in the symptom presentation of study participants and for the presence of other medical comorbidities. In addition, the selected differentially expressed genes were obtained from raw microarray data, basing on our previous finding that using raw microarray data can better generate genetic signatures that are associated with functional pathways that are a priori known for specific medical conditions.39 Future studies should consider using preprocessing techniques, such as Robust Microarray Average, to determine if similar discriminatory genes can be identified.
 

pattismith

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interesting,

looking at my personal genome, I found two heterozygous missense variant involved

-in the HTT gene (huntingtin) 4.23% frequency
-in the MERTK gene (Tyrosine kinase, gene involved in hepatic fibrosis) 4.73% frequency
 

pattismith

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I was thinking about the HHT gene (Huntingtin).


Here a list of Basal Ganglia Diseases (Basal Ganglia sometimes shows up in ME/CFS studies).:


upload_2018-12-16_16-31-55.png



Huntington disease is one of them, and here what wiki sumup about it:

"Huntington’s disease is a hereditary disease that causes defects in behavior, cognition, and uncontrolled rapid, jerky movements.[1] Huntington’s disease stems from a defect that consists of an expanded CAG repeat in a gene located on chromosome 4p.

Evidence shows that the basal ganglias in patients with Huntington’s Disease show a decrease in activity of the mitochondrial pathway, complex II-III. Such deficiencies are often associated with basal ganglia degeneration.[7] This degeneration of striatal neurons projecting to GPe leads to disinhibition of the indirect pathway, increased inhibition of STN, and therefore, reduced output of the basal ganglia.[2]"



If variant in the HTT gene can potentially give a ME/CFS increase risk in some patients, it may be related to this effect on the mitochondria into the basal ganglia.


Interestingly "Adenosine, modulates motor activity by interactions with the dopaminergic system within the basal ganglia", "Adenosine A2A antagonists exert anti-parkinsonian action (Kanda et al., 1998; MuÈ ller, 2000), while adenosine receptor agonists have been suggested as new therapeutics for hyperkinetic basal ganglia disorders"


(Parikinson and hyperkinetic are both diseases affecting Basal Ganglia)


Idem for Huntington that has been linked to adenosine receptors here

"Chronic intake of caffeine (antagonist of adenosine receptors A1 and A2a) was recently shown to be positively associated with the disease onset of Huntington D. Moreover, genetic polymorphism of A2AR is believed to impact the age of onset. Given the importance of adenosine receptors as drug targets for human diseases, this review highlights the recent findings that delineate the roles of adenosine receptors in HD and discusses their potential for serving as drug targets and/or biomarkers for HD."


and here:

"Intrastriatal administration of ENT1 inhibitors increased extracellular level of adenosine in the striatum of R6/2 mice to a much higher level than controls. Chronic inhibition of ENT1 or by genetic removal of ENT1 enhanced the survival of R6/2 mice. Collectively, adenosine homeostasis and ENT1 expression are altered in HD. The inhibition of ENT1 can enhance extracellular adenosine level and be a potential therapeutic approach for treating HD."


My conclusion:

If ME/CFS is linked to a decrease activity in the Basal Ganglia, adenosine receptor agonist may be helpful (Inosine is one), and Caffeine could have worsening effect.