Gene variations could be responsible for about one third of complex regional pain syndrome cases, a new study has found.
Research published today in the Journal of Medical Genetics shows that there may also be sex-specific causes because although the condition is less common in men, they are more likely to have the four genetic variations behind the increased risk.
Most cases of the syndrome are triggered by an injury and while it is difficult to treat, it often improves over time. However, some people suffer intense pain for many years.
In this observational study, the research team, involving scientists from Cambridge University and colleagues from Liverpool and Indonesia, looked at single nucleotide polymorphisms (SNPs) in DNA samples from 34 people diagnosed with CRPS (the discovery group).
These SNPs were also looked for in 39 people with chronic back pain (the comparison group) and then in another 50 people with the syndrome (confirmatory group).
A single SNP in each of the ANO10, P2RX7, PRKAG1 and SLC12A9 genes was more common in those with CRPS in both the discovery and confirmatory groups than it was in the comparison group.
In total, 25 out of 84 (30%) patients who had had CRPS for more than a year expressed these variations in at least one of the four genes. None was found among those in the comparison group.
They found CRPS is more common in men than women, by a ratio of 3-4:1, but more men than women expressed these genetic variations at 8 out of 14 (57%) compared to 17 out of 70 (24%) women.
The researchers write: “This raises the possibility of different mechanisms of disease in males and females and that therapeutic responses may also be influenced by sex.
“We acknowledge that our genetic results may be only part of the story; autoimmune disease is more common in women than men, and recent studies strongly suggest it could be causative in some cases.”
They believe there may be biological explanations for their findings because ANO10, P2RX7and SLC12A9 are expressed in immune cells in the peripheral nervous system, both of which are involved in the types of symptoms seen in people with the syndrome and all four genes are normally expressed in macrophages in healthy people.
No conclusions can be derived from the observational study, but the researchers write: “Our data support an underlying genetic predisposition in up to a third of cases, with this effect being most prominent in males. Further study of these genes and SNPs may catalyse the generation of personalised precision diagnosis and treatments.”
Shaikh SS, Goebel A, Lee MC et al. Evidence of a genetic background predisposing to complex regional pain syndrome type 1. Journal of Medical Genetics 11 October 2023; doi 10.1136/jmg-2023-109236
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