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Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in CFS

Discussion in 'Latest ME/CFS Research' started by mango, Jul 28, 2016.

  1. mango

    mango Senior Member

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    Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.

    Hall KT1,2, Kossowsky J2,3,4, Oberlander TF5, Kaptchuk TJ2,6,7, Saul JP8, Wyller VB9, Fagermoen E10, Sulheim D11, Gjerstad J12, Winger A13, Mukamal KJ2,6.

    Pharmacogenomics J. 2016 Jul 26. doi: 10.1038/tpj.2016.53. [Epub ahead of print]

    Abstract

    Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown.

    Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function.

    A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104).

    Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04).

    There were no differences between clonidine and placebo among patients with COMT low-activity alleles.

    Similar gene-drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine-COMT interaction effects in other conditions.

    DOI: 10.1038/tpj.2016.53

    http://www.ncbi.nlm.nih.gov/pubmed/27457818
     
  2. M Paine

    M Paine Senior Member

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    Auckland, New Zealand
    So, just attempting to decipher this paper...

    The researchers tried treating patients with a drug (Clonidine) which can bind to α2-adrenergic receptors, activating them (agonist), lowering circulating norepinephrine and epinephrine (lessening the sympathetic nervous system fight or flight response).

    No change was observed in most patients. In a subset of patients, their condition worsened. Those patients had mutations in the gene encoding for one of several enzymes (COMT) which degrades norepinephrine and epinephrine.

    Does that sound about right?
     
    Last edited: Jul 28, 2016
  3. Snow Leopard

    Snow Leopard Hibernating

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    rs4680 is included in the 23andme panel. I'm heterozygous...

    The A/A subgroup appears to be an atypical minority of patients, suggested to be associated with higher cortisol, norepinephrine and epinephrine.

    "Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome."
    http://www.ncbi.nlm.nih.gov/pubmed/26272340
    (Note: the above study showed no difference in prevalence between healthy controls and patients)

    "Polymorphisms of Adrenergic Cardiovascular Control Genes are Associated with Adolescent Chronic Fatigue Syndrome"
    http://www.ncbi.nlm.nih.gov/pubmed/21059181
     
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  4. Valentijn

    Valentijn WE ARE KINA

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    I'd be surprised if they were much of a minority. About 50% of people have A/G, 25% have A/A, and 25% have G/G.

    It might just be a case of sub-dividing the patients and looking at more variables until something shows statistical significance, which will randomly happen eventually anyhow.

    I'm also not sure what the point is of further research with the drug. No one was helped by it, and the apparently interesting aspect is that it (might have) made some people sicker. Sounds fun :p
     
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  5. Sidereal

    Sidereal Senior Member

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    When is this research group going to grasp the possibility that the high sympathetic activity (which is far from a universal finding in those diagnosed with ME/CFS) is a compensation to the low energy state? They keep putting out these clonidine papers.
     
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