Most patients do not currently have access to measure gene *expression*, which is more significant than the genes themselves. Lifestyle factors such as childhood trauma, nutrition, stress and toxic exposure modify the expression of genes.
For gene testing, see 23 & me or others.
SNPs (2006): only 28 out of several million possible SNPs predict whether a person has CFS with 76% accuracy, those responsible for brain function, stress reactions, emotional responses, generation, and maintenance of memory. The top three genes containing the SNPs accounting for the highest accumulated importances were neuronal tryptophan hydroxylase (TPH2), catechol-O-methyltransferase (COMT) and nuclear receptor subfamily 3, group C, member 1 glucocorticoid receptor (NR3C1).
serotonin: HTR2A variants: the A allele of -1438G/A (rs6311)
creates a consensus binding site for Th1/E47, a transcription factor implicated in the development of the nervous system.
exercise: : In 71%, exercise increased sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48h, correlated with behavioural measures of fatigue and pain. In the other 29% of patients with CFS, adrenergic α-2A receptor’s transcription was decreased at all time-points after exercise only; history of orthostatic intolerance was significantly more common in the α-2A decrease subgroup.
adrenergic A2A receptors same prior to exercise, expression after exercise is increased in association with physical and mental fatigue and pain. (Changes in amounts of mRNA)
NEW SNPs in the gene for TRPM3, a calcium ion channel.
2 mutations in that gene
It is a steroid mechanism of action site, and also the point of action of verapamil and mefanimic acid. It is important in natural killer cell function too.
We are trying to work out how to modify it. Calcium (main activator) competes with magnesium — so a magnesium supplement may help.
VDR Taq gene- vitamin d?
rs6323: down or upregulates MAO-A production which in turn is responsible for breakdown of catecholamines (serotonin, dopamine etc).
COMT c677t
HLA genes for autoimmunity (celiac) and Lyme/mold issues (shoemaker), being further investigated by Ron Davis and Stanford
Metabolomics- increased gene expressions (sRNA) of PD kinase that inhibits PDH
7/8 subtypes by genome
Holistic Myalgic Encephalomyelitis 