Shaikh, Samiha S, Goebel, Andreas 
ORCID: 0000-0002-3763-8206, Lee, Michael C, Nahorski, Michael S, Shenker, Nicholas, Pamela, Yunisa, Drissi, Ichrak, Brown, Christopher ORCID: 0000-0003-1414-2635, Ison, Gillian, Shaikh, Maliha F et al (show 7 more authors)
(2023)
Evidence of a genetic background predisposing to complex regional pain syndrome type 1.
Journal of medical genetics, 61 (2).
jmg-2023-109236-jmg-2023-109236.
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Abstract
<h4>Background</h4>Complex regional pain syndrome type 1 (CRPS-1) is a rare, disabling and sometimes chronic disorder usually arising after a trauma. This exploratory study examined whether patients with chronic CRPS-1 have a different genetic profile compared with those who do not have the condition.<h4>Methods</h4>Exome sequencing was performed to seek altered non-synonymous SNP allele frequencies in a discovery cohort of well-characterised patients with chronic CRPS-1 (n<i>=</i>34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n<i>=</i>50). Gene expression of peripheral blood macrophages was assessed.<h4>Results</h4>In the discovery cohort, the rare allele frequencies of four non-synonymous SNPs were statistically increased. The replication cohort confirmed this finding. In a chronic pain cohort, these alleles were not overexpressed. In total, 25 out of 84 (29.8%) patients with CRPS-1 expressed a rare allele. The SNPs were rs41289586 in <i>ANO10</i>, rs28360457 in <i>P2RX7</i>, rs1126930 in <i>PRKAG1</i> and rs80308281 in <i>SLC12A9</i>. Males were more likely than females to have a rare SNP allele, 8 out of 14 (57.1%) vs 17 out of 70 (24.3%) (Fisher's p=0.023). <i>ANO10</i>, <i>P2RX7</i>, <i>PRKAG1</i> and <i>SLC12A9</i> were all expressed in macrophages from healthy human controls.<h4>Conclusion</h4>A single SNP in each of the genes <i>ANO10, P2RX7, PRKAG1</i> and <i>SLC12A9</i> was associated with developing chronic CRPS-1, with more males than females expressing these rare alleles. Our work suggests the possibility that a permissive genetic background is an important factor in the development of CRPS-1.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Genetic Predisposition to Disease, Genetics, Medical, Genetic Variation, Human Genetics, Mutation, Missense |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 16 Oct 2023 08:31 |
| Last Modified: | 02 Feb 2024 10:31 |
| DOI: | 10.1136/jmg-2023-109236 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173723 |
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