Severe ME Day of Understanding and Remembrance: Aug. 8, 2017
Determined to paper the Internet with articles about ME, Jody Smith brings some additional focus to Severe Myalgic Encephalomyelitis Day of Understanding and Remembrance on Aug. 8, 2017 ...
Discuss the article on the Forums.

A genome association study of TRP ion channels, ACh receptors, and adrenergic receptors in ME/CFS

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

  1. hixxy

    hixxy Senior Member

    Messages:
    1,121
    Likes:
    1,293
    Australia
    BMC Med Genet. 2016 Nov 11;17(1):79.

    A targeted genome association study examining transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

    Johnston S 1,2, Staines D 3, Klein A 4,3, Marshall-Gradisnik S 4,3.

    Abstract

    BACKGROUND:
    Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (CFS/ME) is a debilitating condition of unknown aetiology. It is characterized by a range of physiological effects including neurological, sensory and motor disturbances. This study examined candidate genes for the above clinical manifestations to identify single nucleotide polymorphism (SNP) alleles associated with CFS/ME compared with healthy controls.

    METHODS:
    DNA was extracted and whole genome genotyping was performed using the HumanOmniExpress BeadChip array. Gene families for transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors, and acetylcholinesterase were targeted. The frequency of each SNP and their association between CFS/ME and healthy controls was examined using Fisher's exact test, and to adjust for multiple testing, False Detection Rate (FDR) and Bonferroni corrections were applied (p < 0.05).

    RESULTS:
    The study included 172 participants, consisting of 95 Fukuda defined CFS/ME patients (45.8 ± 8.9; 69 % female) and 77 healthy controls (42.3 ± 10.3; 63 % female). A total of 950 SNPs were included for analysis. 60 significant SNPs were associated with CFS/ME compared with healthy controls. After applying FDR and Bonferroni corrections, SNP rs2322333 in adrenergic receptor α1 (ADRA1A) was higher in CFS/ME compared with healthy controls (45.3 % vs. 23.4 %; p = 0.059). The genotype class that was homozygous minor (AA) was substantially lower in CFS/ME compared with healthy controls (4.2 % vs. 24.7 %).

    CONCLUSIONS:
    This study reports for the first time the identification of ADRA1A and a possible association between CFS/ME and genotype classes. Further examination of the functional role of this class of adrenergic receptors may elucidate the cause of particular clinical manifestations observed in CFS/ME.

    KEYWORDS:
    Adrenergic receptors; Chronic fatigue syndrome; Genome association; Myalgic encephalomyelitis; Single nucleotide polymorphisms

    PMID: 27835969
    DOI: 10.1186/s12881-016-0342-y

    https://www.ncbi.nlm.nih.gov/pubmed/27835969
    http://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-016-0342-y
     
    Theodore likes this.
  2. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    They finally seem to have gotten the message about needing to correct for multiple comparisons in their SNP studies.

    When they do, and with an increased sample size (though still small for a good genetic study), they are left with a single SNP, and even that is not really significant.

    They have just negated all their previous publications on TRP ion channels, ACh receptors etc and fudged this single result.

    I am so disappointed in the research coming out of this group. Their abysmal SNP studies undermine confidence in their other work and give CFS/ME research a bad name.
     
    simeyss, ukxmrv, A.B. and 3 others like this.
  3. Gamboa

    Gamboa Senior Member

    Messages:
    258
    Likes:
    468
    Canada
    I'm having trouble understanding whether homozygous AA or GG associated with ME/CFS.

    I checked my own results and am GG for ADRA1A rs2322333 ( 23 and me raw data).
     
  4. hixxy

    hixxy Senior Member

    Messages:
    1,121
    Likes:
    1,293
    Australia
    Moreover, the genotype class that was homozygous minor (AA) was much lower in CFS/ME patients compared with healthy controls (4.2 % vs. 24.7 %).

    So the paper asserts that AA is not associated with ME/CFS.
     
  5. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,814
    So they're saying that the more common allele was even more common in ME patients :bang-head: Except even that wasn't statistically significant.

    Glad to see them correcting for multiple comparisons, but the ultimate message is that this SNP probably isn't relevant, and is just a false positive.
     
  6. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,613
    Likes:
    12,437
    South Australia
    Another false positive in a candidate gene association study (why do people still do these studies when false positives are so common?). Nothing to see here, move along.
     
    Valentijn likes this.
  7. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,133
    Likes:
    3,822
    Bristol
    There's also this in the same ncbi email:

    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 S1,2, Johnston S3,2, Chacko A3,2, Nguyen T3,2, Smith P2, Staines D3,2.
    Author information:

    • 2The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
    • 3School of Medical Science, Griffith University, Gold Coast, QLD, Australia.


    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.
     
  8. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,133
    Likes:
    3,822
    Bristol
    I don't think it is from the same study. Just coincidence?

    My brainfog is too bad to attempt to read it properly. Does this one say anything of interest @alicec @Valentijn @Snow Leopard @hixxy ?
     
    Last edited: Nov 14, 2016
    Paintmyturquoise likes this.
  9. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    It is nonsense. Here is a post.
     
  10. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,133
    Likes:
    3,822
    Bristol
    Yes DNA is the same all over your body isn't it! Type of thing that with brainfog I assume I've misunderstood.
     
  11. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,814
    There can be changes due to new mutations, but those are typically very limited to one tiny area. And it still doesn't make sense in the context of these research papers :p
     
    Jenny TipsforME likes this.

See more popular forum discussions.

Share This Page