• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

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

hixxy

Senior Member
Messages
1,229
Location
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
 

alicec

Senior Member
Messages
1,572
Location
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.
 

Gamboa

Senior Member
Messages
261
Location
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).
 

hixxy

Senior Member
Messages
1,229
Location
Australia
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).

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.
 
Messages
15,786
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 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.
 

Jenny TipsforME

Senior Member
Messages
1,184
Location
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.