Evidence of a genetic background predisposing to complex regional pain syndrome type 1
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ..
BACKGROUND: 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.
METHODS: 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=34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n=50). Gene expression of peripheral blood macrophages was assessed.
RESULTS: 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 ANO10, rs28360457 in P2RX7, rs1126930 in PRKAG1 and rs80308281 in SLC12A9. 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). ANO10, P2RX7, PRKAG1 and SLC12A9 were all expressed in macrophages from healthy human controls.
CONCLUSION: A single SNP in each of the genes ANO10, P2RX7, PRKAG1 and SLC12A9 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
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| Enthalten in: |
Journal of medical genetics - 61(2024), 2 vom: 19. Jan., Seite 163-170 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shaikh, Samiha S [VerfasserIn] |
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| Links: |
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| Themen: |
Genetic Predisposition to Disease |
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| Anmerkungen: |
Date Completed 22.01.2024 Date Revised 21.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1136/jmg-2023-109236 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Shaikh, Samiha S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evidence of a genetic background predisposing to complex regional pain syndrome type 1 |
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| 500 | |a Date Revised 21.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: 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=34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n=50). Gene expression of peripheral blood macrophages was assessed | ||
| 520 | |a RESULTS: 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 ANO10, rs28360457 in P2RX7, rs1126930 in PRKAG1 and rs80308281 in SLC12A9. 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). ANO10, P2RX7, PRKAG1 and SLC12A9 were all expressed in macrophages from healthy human controls | ||
| 520 | |a CONCLUSION: A single SNP in each of the genes ANO10, P2RX7, PRKAG1 and SLC12A9 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Genetic Predisposition to Disease | |
| 650 | 4 | |a Genetic Variation | |
| 650 | 4 | |a Genetics, Medical | |
| 650 | 4 | |a Human Genetics | |
| 650 | 4 | |a Mutation, Missense | |
| 700 | 1 | |a Goebel, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Nahorski, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Shenker, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Pamela, Yunisa |e verfasserin |4 aut | |
| 700 | 1 | |a Drissi, Ichrak |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Ison, Gillian |e verfasserin |4 aut | |
| 700 | 1 | |a Shaikh, Maliha F |e verfasserin |4 aut | |
| 700 | 1 | |a Kuttikat, Anoop |e verfasserin |4 aut | |
| 700 | 1 | |a Woods, William A |e verfasserin |4 aut | |
| 700 | 1 | |a Dixit, Abhishek |e verfasserin |4 aut | |
| 700 | 1 | |a Stouffer, Kaitlin |e verfasserin |4 aut | |
| 700 | 1 | |a Clarke, Murray Ch |e verfasserin |4 aut | |
| 700 | 1 | |a Menon, David K |e verfasserin |4 aut | |
| 700 | 1 | |a Woods, C Geoffrey |e verfasserin |4 aut | |
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