Epigenetic signature of chronic low back pain in human T cells

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:. G...

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Autores principales: Stéphanie Grégoire, David Cheishvili, Mali Salmon-Divon, Sergiy Dymov, Lucas Topham, Virginie Calderon, Yoram Shir, Moshe Szyf, Laura S. Stone
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Publicado: Wolters Kluwer 2021
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spelling oai:doaj.org-article:834bfd8300a94aec92e6c133920966ed2021-11-25T07:59:39ZEpigenetic signature of chronic low back pain in human T cells2471-253110.1097/PR9.0000000000000960https://doaj.org/article/834bfd8300a94aec92e6c133920966ed2021-11-01T00:00:00Zhttp://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000960https://doaj.org/toc/2471-2531Abstract. 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.Stéphanie GrégoireDavid CheishviliMali Salmon-DivonSergiy DymovLucas TophamVirginie CalderonYoram ShirMoshe SzyfLaura S. StoneWolters KluwerarticleAnesthesiologyRD78.3-87.3ENPAIN Reports, Vol 6, Iss 4, p e960 (2021)
institution DOAJ
collection DOAJ
language EN
topic Anesthesiology
RD78.3-87.3
spellingShingle Anesthesiology
RD78.3-87.3
Stéphanie Grégoire
David Cheishvili
Mali Salmon-Divon
Sergiy Dymov
Lucas Topham
Virginie Calderon
Yoram Shir
Moshe Szyf
Laura S. Stone
Epigenetic signature of chronic low back pain in human T cells
description 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.
format article
author Stéphanie Grégoire
David Cheishvili
Mali Salmon-Divon
Sergiy Dymov
Lucas Topham
Virginie Calderon
Yoram Shir
Moshe Szyf
Laura S. Stone
author_facet Stéphanie Grégoire
David Cheishvili
Mali Salmon-Divon
Sergiy Dymov
Lucas Topham
Virginie Calderon
Yoram Shir
Moshe Szyf
Laura S. Stone
author_sort Stéphanie Grégoire
title Epigenetic signature of chronic low back pain in human T cells
title_short Epigenetic signature of chronic low back pain in human T cells
title_full Epigenetic signature of chronic low back pain in human T cells
title_fullStr Epigenetic signature of chronic low back pain in human T cells
title_full_unstemmed Epigenetic signature of chronic low back pain in human T cells
title_sort epigenetic signature of chronic low back pain in human t cells
publisher Wolters Kluwer
publishDate 2021
url https://doaj.org/article/834bfd8300a94aec92e6c133920966ed
work_keys_str_mv AT stephaniegregoire epigeneticsignatureofchroniclowbackpaininhumantcells
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