CFS/ME vs Mitochondrial Dysfunction

This paper is a totally different take on mitochondria's role in CFS/ME than the standard idea brought forth by Dr. Myhill (mito ATP is broken and needs repair).  Of note, Dr Myhill is a general practitioner who treats patients in a regular clinical setting and is not a researcher per say.  This paper was done by genetics researchers using patient data from a central database.  Okay with that caveat let's proceed...

If.  IF! I am reading this paper correctly, then the authors looked at three things in the mitochondria (mito) of PWME/CFS and age/sex matched controls: the haplogroups, SNPs and heteroplasmy.  Think of haplogroups as the ancestral lines of the mito DNA.  If you come from the UK you will have slightly different mito DNA than someone that comes from Asia.  These lines can be traced back for thousands of years over hundreds of generations.  As an aside, the lineage of humans was traced back through maternal mito DNA.

SNPs are single nucleotide polymorphisms which are single locations on a gene.  Each location can have one of two proteins that encodes the genetic information for accurate cell reproduction or genetic recipe if you will.  A single SNP error can potentially lead to illness or disease but not always as the body often has work arounds and redundant systems in place to ensure survival despite coding errors.  A single disease often has clusters of SNP associated with it rather than a single SNP.

Heteroplasmy is the case where a single cell has mitochondria with different types of DNA.  Sometimes this diversity is good and can lead to long life and other times it can lead to disease.  I know too little about this in general to add to this.  Right now this is just paraphrased from the wiki entry on heteroplasmy.

So, this study looked at the ancestry of the mito DNA, the single genetic errors in the mito DNA and the number of different types of mito DNA in patients.  And some very interesting data popped out:

• when all the variables are adjusted for there are no specific SNPs associated with CFS/ME
• there were no significant differences in the heteroplasmy of CFS/ME patients and healthy controls
• This is the interesting bit: while there were no significant differences between CFS/ME patients and healthy controls with regard to haplotype, each haplotype is predictive of the subclass of CFS/ME patients.  In other words, while a single or combination of haplotypes could not predict illness necessarily happening it could predict the symptoms once illness is present.  So one haplotype would have more neuro symptoms, while another would have more gastric symptoms while a third would have more energy production problems.  Wicked cool!!

The significance of these results is that...

 "The variation in symptom constellation that occurs in ME/CFS could be due to genetic variation in individuals, rather than differences in underlying cause of the disease."

which is VERY important to understand.  While there seems to be no difference in mitochondrial DNA between the sick folk and controls, the mito DNA haplotypes do affect how the illness presents itself.

Of course this research needs to be duplicated to be confirmed but it is super cool none the less.

Here is the link to the very technical paper:

Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome  Paul Billing-Ross^1†, Arnaud Germain^2†, Kaixiong Ye³, Alon Keinan³, Zhenglong Gu¹ andMaureen R. Hanson^2*