Increased prevalence of two mitochondrial DNA polymorphisms in functional disease

[allyb]

Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant?

Jonathan Kerr et al.....

Abstract
About 20% of the population suffers from "functional syndromes". Since these syndromes overlap greatly in terms of co-morbidity, pathophysiology (including aberrant autonomic activity) and treatment responses, common predisposing genetic factors have been postulated. We had previously showed that two common mitochondrial DNA (mtDNA) polymorphisms at positions 16519 and 3010 are statistically associated with the functional syndromes of migraine, cyclic vomiting syndrome and non-specific abdominal pain. Herein, among individuals with mtDNA haplogroup H (HgH), the presence of these two mtDNA polymorphisms were ascertained in additional functional syndromes: chronic fatigue syndrome, complex regional pain syndrome, sudden infant death syndrome, and major depressive disorder. Polymorphic prevalence rates were compared between disease and control groups, and within each disease group in participants with and without specific clinical findings. In all four conditions, one or both of the polymorphisms was significantly associated with the respective condition and/or co-morbid functional symptomatology. Thus, we conclude that these two mtDNA polymorphisms likely modify risk for the development of multiple functional syndromes, likely constituting a proportion of the postulated common genetic factor, at least among individuals with HgH. Pathophysiology likely involves broad effects on the autonomic nervous system.

http://www.ncbi.nlm.nih.gov/pubmed/25934187

 

[Valentijn]

About 25% of Europeans have the "A" allele at MTDNA 3010 (rs3928306), which defines the H1 and J1 maternal haplogroups. Of the 46 European ME/SEID patients for whom I have 23andMe data, 13 have the A allele at 3010, or 28.3%. So it's looking pretty normal for us as a group, though that's without taking specific symptoms into account beyond what is required for an ME diagnosis.

16519 T doesn't seem to have a strong connection to specific haplogroups, for the most part. Nonetheless, for the 31 patients I have full data for, 6 have the T allele, as do 6 of the controls matched by maternal haplogroup. 4 of the patients with the T allele also have their specific controls with the T allele, but 3 patients' control do not match up for the allele despite having an identical haplogroup, and another's patient control also does not match but has a somewhat different haplogroup from the patient due to no very close matches being available.

So basically, rates of these two SNPs are looking quite normal for us. And neither is a coding SNP, so is not resulting in alterations to the structure or sequence of any proteins being created. Though it is possible that they have a regulatory role.

 

[Marco]

@Valentijn

You're probably right and there's little direct evidence of mitochondrial disease in ME/CFS but its interesting that those odd eyesight problems involving 'ocular motility' found in ME/CFS also show up in mito disease (but probably also in other diseases affecting certain brain regions).

http://www.meresearch.org.uk/our-research/completed-studies/eye-movement-dysfunction/

http://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2010.01865.x/full

 

[Valentijn]

You're probably right and there's little direct evidence of mitochondrial disease in ME/CFS but its interesting that those odd eyesight problems involving 'ocular motility' found in ME/CFS also show up in mito disease (but probably also in other diseases affecting certain brain regions).

My eye problems only manifest when generally or visually exhausted. So my interpretation is that it's pretty much just another muscle getting "overused" and worn out at times, rather than a specific ocular problem.

 

[Kyla]

How can something be both "functional" and explained by genetics at the same time?
Isn't the entire definition of "functional" disorders that they cannot be explained by biological abnormalities?

This seems like some very fancy footwork to keep this category of diagnosis alive in the face of competing evidence.

 

[Sea]

How can something be both "functional" and explained by genetics at the same time?
Isn't the entire definition of "functional" disorders that they cannot be explained by biological abnormalities?

This seems like some very fancy footwork to keep this category of diagnosis alive in the face of competing evidence.

I think functional is one of those terms that can mean different things to different people. For some they mean psychosomatic, for others they simply mean unexplained, as in symptoms are acknowledged but nothing physically wrong has been found. The researchers who are interested keep looking for an explanation that is not psychological.

Eg in IBS where a colonoscopy/endoscopy/biopsy has found no intestinal damage, inflammation or infection some gastros would use the term functional without dismissing that there is actually something physically wrong that just hasn't been discovered yet.

 

[alex3619]

How can something be both "functional" and explained by genetics at the same time?
Isn't the entire definition of "functional" disorders that they cannot be explained by biological abnormalities?

This seems like some very fancy footwork to keep this category of diagnosis alive in the face of competing evidence.

My prediction is that all (psychiatric) functional syndromes will be proven to be physical in the long run. Its a wastebasket diagnosis. Its also conflating the issue of physical functional disorders with psychiatric functional disorders.

The term "functional" is an overloaded term, just like "recovery" and "normal". That means it has multiple meanings that are context dependent and are a means for psychiatrists to lie to patients.