Epigenetic signature of chronic low back pain in human T cells

Stéphanie Grégoire; David Cheishvili; Mali Salmon-Divon; Sergiy Dymov; Lucas Topham; Virginie Calderon; Yoram Shir; Moshe Szyf; Laura S Stone

doi:10.1097/PR9.0000000000000960

Epigenetic signature of chronic low back pain in human T cells

Pain Rep. 2021 Nov 3;6(4):e960. doi: 10.1097/PR9.0000000000000960. eCollection 2021 Nov-Dec.

Authors

Stéphanie Grégoire^{1

2}, David Cheishvili^{3

4

5}, Mali Salmon-Divon^{5

6}, Sergiy Dymov⁶, Lucas Topham^{1

2}, Virginie Calderon⁷, Yoram Shir^{1

8

9}, Moshe Szyf^{3

6

10}, Laura S Stone^{1

2

6

8

11

12}

Affiliations

¹ Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
² Faculty of Dentistry, McGill University, Montreal, QC, Canada.
³ HKG Epitherapeutics, Honk Kong, China.
⁴ Department of Oncology, McGill University, Montreal, QC, Canada.
⁵ Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel.
⁶ Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
⁷ Institut de Recherches Cliniques de Montréal, Montreal, QC, Canada.
⁸ Department of Anesthesiology, McGill University, Montreal, QC, Canada.
⁹ Alan Edwards Pain Management Unit, Montreal General Hospital, Montreal, QC, Canada.
¹⁰ Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, Canada.
¹¹ Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
¹² Department of Anesthesiology, University of Minnesota, Minneapolis, MN, USA.

Abstract

Objective: Determine if chronic low back pain (LBP) is associated with DNA methylation signatures in human T cells that will reveal novel mechanisms and potential therapeutic targets and explore the feasibility of epigenetic diagnostic markers for pain-related pathophysiology.

Methods: Genome-wide DNA methylation analysis of 850,000 CpG sites in women and men with chronic LBP and pain-free controls was performed. T cells were isolated (discovery cohort, n = 32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified. A polygenic DNA methylation score for LBP was generated in both women and men. Validation was performed in an independent cohort (validation cohort, n = 63) of chronic LBP and healthy controls.

Results: Analysis with the discovery cohort revealed a total of 2,496 and 419 differentially methylated CpGs in women and men, respectively. In women, most of these sites were hypomethylated and enriched in genes with functions in the extracellular matrix, in the immune system (ie, cytokines), or in epigenetic processes. In men, a unique chronic LBP DNA methylation signature was identified characterized by significant enrichment for genes from the major histocompatibility complex. Sex-specific polygenic DNA methylation scores were generated to estimate the pain status of each individual and confirmed in the validation cohort using pyrosequencing.

Conclusion: This study reveals sex-specific DNA methylation signatures in human T cells that discriminates chronic LBP participants from healthy controls.

Keywords: Biomarker; DNA methylation; Epigenetics; Low back pain; T cells.