DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/A polymorphism). "Dna-SNP" by SNP model by David Eccles (gringer).

DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/A polymorphism).

Human beings are 99.5% identical as regards their DNA gene sequences. The remaining 0.5% mainly consists of single nucleotide polymorphisms (SNPs, pronounced “snips”), which are small genetic changes in DNA that vary between individuals. Most SNPs are silent, but others have important consequences; a single SNP mutation in the APOE gene, for example, is associated with an increased risk of Alzheimer’s disease. At the moment, scientists across the world are involved in identifying particular SNPs and linking them with particular diseases.

To date, only a handful of studies have attempted to examine individual SNPs or patterns of SNPs in ME/CFS patients. One was an ME Research UK-funded investigation at the University of London, which found significant differences in the distribution of a small number of gene SNPs between ME/CFS patients and healthy people (see report). Another study, from Japan, examined SNPs in genes involved in the monoaminergic system but did not find an association overall (abstract), while an investigation by the Center for Disease Control in Atlanta, Georgia found that genes associated with glutamatergic neurotransmission and circadian rhythm might be associated with ME/CFS (abstract).

The latest report on SNPs in ME/CFS is a pilot study from Griffith University, Australia, and it focuses on the transient receptor potential (TRP) ‘superfamily’ of ion channels involved in many key biological processes. TRPs are known to be impaired in a range of diseases, including chronic pain and motor neuropathy, so it is certainly feasible that there might be specific variations in SNPs associated with TRP ion channel genes in people with ME/CFS.

When the Australian researchers compared 115 ME/CFS patients and 90 ‘non-fatigued’ controls, they found that 13 SNPs were present at significantly different frequencies. Nine of these SNPs were associated with the TRPM3 gene, located on chromosome number 9, which makes a protein involved in cellular calcium signalling and in maintaining physiologically stable conditions (homeostasis). Of the others, two were associated with TRPA1 (a sensor for pain, stretch and environmental irritants) and two with TRPC4 which plays a part in the regulation of blood vessels and cell division. As the researchers point out, the results of this pilot study are essentially preliminary, though they do imply that genetic alterations at TRP ion channels have a role in the development or maintenance of ME/CFS.

All the investigations on SNPs in ME/CFS that have been published to date can best be described as ‘hypothesis-generating’ rather than conclusive in themselves. Their aim is to pin-point specific areas of the genome that future investigations might examine more closely. However, complex chronic illnesses like ME/CFS are most likely to be the result of very large numbers of SNP variants working in concert. So, in reality, large studies using genome-wide scanning methodologies and complex analytical methods will be required to obtain definitive results (see a recent review). At present, the ‘SNP500Cancer’ project is examining samples to locate SNPs of immediate importance to molecular epidemiology studies in cancer, and there are many such examples in a range of illnesses. Ideally, there would be a ‘SNPMEproject’ using state-of-the-art techniques to do the same for ME/CFS.

Further reading
Examination of single nucleotide polymorphisms (SNPs) in transient receptor potential (TRP) ion channels in chronic fatigue syndrome patients. Marshall-Gradisnik SM, et al. Immunology and Immunogenetics Insights, 2015 May 10. Read more (full text).

Use of single-nucleotide polymorphisms (SNPs) to distinguish gene expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Read more.

SNPs – A shortcut to personalized medicine, by Bruce Carlson

Genomics in Cardiovascular Disease. Roberts R, et al. Journal of the American College of Cardiology, 2013 May 21. Read more.

Photo credit
Dna-SNP” by SNP model by David Eccles (gringer).