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DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury.

Publication ,  Journal Article
Bruehl, S; Gamazon, ER; Van de Ven, T; Buchheit, T; Walsh, CG; Mishra, P; Ramanujan, K; Shaw, A
Published in: Pain
October 2019

Factors contributing to development of complex regional pain syndrome (CRPS) are not fully understood. This study examined possible epigenetic mechanisms that may contribute to CRPS after traumatic injury. DNA methylation profiles were compared between individuals developing CRPS (n = 9) and those developing non-CRPS neuropathic pain (n = 38) after undergoing amputation following military trauma. Linear Models for Microarray (LIMMA) analyses revealed 48 differentially methylated cytosine-phosphate-guanine dinucleotide (CpG) sites between groups (unadjusted P's < 0.005), with the top gene COL11A1 meeting Bonferroni-adjusted P < 0.05. The second largest differential methylation was observed for the HLA-DRB6 gene, an immune-related gene linked previously to CRPS in a small gene expression study. For all but 7 of the significant CpG sites, the CRPS group was hypomethylated. Numerous functional Gene Ontology-Biological Process categories were significantly enriched (false discovery rate-adjusted q value <0.15), including multiple immune-related categories (eg, activation of immune response, immune system development, regulation of immune system processes, and antigen processing and presentation). Differentially methylated genes were more highly connected in human protein-protein networks than expected by chance (P < 0.05), supporting the biological relevance of the findings. Results were validated in an independent sample linking a DNA biobank with electronic health records (n = 126 CRPS phenotype, n = 19,768 non-CRPS chronic pain phenotype). Analyses using PrediXcan methodology indicated differences in the genetically determined component of gene expression in 7 of 48 genes identified in methylation analyses (P's < 0.02). Results suggest that immune- and inflammatory-related factors might confer risk of developing CRPS after traumatic injury. Validation findings demonstrate the potential of using electronic health records linked to DNA for genomic studies of CRPS.

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Published In

Pain

DOI

EISSN

1872-6623

Publication Date

October 2019

Volume

160

Issue

10

Start / End Page

2328 / 2337

Location

United States

Related Subject Headings

  • Veterans
  • Male
  • Humans
  • Hospitals, Veterans
  • Genetic Profile
  • Female
  • Epigenesis, Genetic
  • DNA Methylation
  • Complex Regional Pain Syndromes
  • Combat Disorders
 

Citation

APA
Chicago
ICMJE
MLA
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Bruehl, S., Gamazon, E. R., Van de Ven, T., Buchheit, T., Walsh, C. G., Mishra, P., … Shaw, A. (2019). DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury. Pain, 160(10), 2328–2337. https://doi.org/10.1097/j.pain.0000000000001624
Bruehl, Stephen, Eric R. Gamazon, Thomas Van de Ven, Thomas Buchheit, Colin G. Walsh, Puneet Mishra, Krishnan Ramanujan, and Andrew Shaw. “DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury.Pain 160, no. 10 (October 2019): 2328–37. https://doi.org/10.1097/j.pain.0000000000001624.
Bruehl S, Gamazon ER, Van de Ven T, Buchheit T, Walsh CG, Mishra P, et al. DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury. Pain. 2019 Oct;160(10):2328–37.
Bruehl, Stephen, et al. “DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury.Pain, vol. 160, no. 10, Oct. 2019, pp. 2328–37. Pubmed, doi:10.1097/j.pain.0000000000001624.
Bruehl S, Gamazon ER, Van de Ven T, Buchheit T, Walsh CG, Mishra P, Ramanujan K, Shaw A. DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury. Pain. 2019 Oct;160(10):2328–2337.

Published In

Pain

DOI

EISSN

1872-6623

Publication Date

October 2019

Volume

160

Issue

10

Start / End Page

2328 / 2337

Location

United States

Related Subject Headings

  • Veterans
  • Male
  • Humans
  • Hospitals, Veterans
  • Genetic Profile
  • Female
  • Epigenesis, Genetic
  • DNA Methylation
  • Complex Regional Pain Syndromes
  • Combat Disorders