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SNPs and genotypes of TRP ion channel and AChR genes from isolated B lymphocytes in ME/CFS

Discussion in 'Latest ME/CFS Research' started by hixxy, Nov 12, 2016.

  1. hixxy

    hixxy Senior Member

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    J Int Med Res. 2016 Nov 10. pii: 0300060516671622. [Epub ahead of print]

    Single nucleotide polymorphisms and genotypes of transient receptor potential ion channel and acetylcholine receptor genes from isolated B lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome patients.

    Marshall-Gradisnik S 1,2, Johnston S 3,2, Chacko A 3,2, Nguyen T 3,2, Smith P 2, Staines D 3,2.

    Abstract

    OBJECTIVE:
    The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca2+) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients.

    METHODS:
    A total of 11 CFS/ME patients (aged 31.82 ± 5.50 years) and 11 non-fatigued controls (aged 33.91 ± 5.06 years) were included. Flow cytometric protocols were used to determine B cell purity, followed by SNP and genotype analysis for 21 mammalian TRP ion channel genes and nine mammalian ACh receptor genes. SNP association and genotyping analysis were performed using ANOVA and PLINK analysis software.

    RESULTS:
    Seventy-eight SNPs were identified in nicotinic and muscarinic acetylcholine receptor genes in the CFS/ME group, of which 35 were in mAChM3. The remaining SNPs were identified in nAChR delta (n = 12), nAChR alpha 9 (n = 5), TRPV2 (n = 7), TRPM3 (n = 4), TRPM4 (n = 1) mAChRM3 2 (n = 2), and mAChRM5 (n = 3) genes. Nine genotypes were identified from SNPs in TRPM3 (n = 1), TRPC6 (n = 1), mAChRM3 (n = 2), nAChR alpha 4 (n = 1), and nAChR beta 1 (n = 4) genes, and were located in introns and 3' untranslated regions. Odds ratios for these specific genotypes ranged between 7.11 and 26.67 for CFS/ME compared with the non-fatigued control group.

    CONCLUSION:
    This preliminary investigation identified a number of SNPs and genotypes in genes encoding TRP ion channels and AChRs from B cells in patients with CFS/ME. These may be involved in B cell functional changes, and suggest a role for Ca2+dysregulation in AChR and TRP ion channel signalling in the pathomechanism of CFS/ME.

    © The Author(s) 2016.

    KEYWORDS:
    B lymphocytes; Transient receptor potential ion channels; acetylcholine; chronic fatigue syndrome; muscarinic receptor; single nucleotide polymorphisms

    PMID: 27834303
    DOI: 10.1177/0300060516671622

    https://www.ncbi.nlm.nih.gov/pubmed/27834303
    http://imr.sagepub.com/content/early/2016/11/09/0300060516671622.full
     
  2. alicec

    alicec Senior Member

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    This is another useless and misleading study from this group which seems to be all about adding a publication to their list.

    They have pulled this stunt several times - analysing SNPs in a subpopulation of cells (previously it was PBMCs and NK cells) as though this has some meaning for the function of those particular cells.

    In reality the SNPs are genome wide and are the same in all cells.

    Here is a post I made about the NK cell study. It applies equally to this one.
     
    Sidereal and Valentijn like this.

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