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Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain

Chronic low back pain (cLBP) that cannot be attributable to a specific pathoanatomical change is associated with high personal and societal costs. Still, the underlying mechanism that causes and sustains such a phenotype is largely unknown. Emerging evidence suggests that epigenetic changes play a r...

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Autores principales: Aroke, Edwin N, Overstreet, Demario S, Penn, Terence M, Crossman, David K, Jackson, Pamela, Tollefsbol, Trygve O, Quinn, Tammie L, Yi, Nengjun, Goodin, Burel R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658508/
https://www.ncbi.nlm.nih.gov/pubmed/33169629
http://dx.doi.org/10.1177/1744806920972889
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author Aroke, Edwin N
Overstreet, Demario S
Penn, Terence M
Crossman, David K
Jackson, Pamela
Tollefsbol, Trygve O
Quinn, Tammie L
Yi, Nengjun
Goodin, Burel R
author_facet Aroke, Edwin N
Overstreet, Demario S
Penn, Terence M
Crossman, David K
Jackson, Pamela
Tollefsbol, Trygve O
Quinn, Tammie L
Yi, Nengjun
Goodin, Burel R
author_sort Aroke, Edwin N
collection PubMed
description Chronic low back pain (cLBP) that cannot be attributable to a specific pathoanatomical change is associated with high personal and societal costs. Still, the underlying mechanism that causes and sustains such a phenotype is largely unknown. Emerging evidence suggests that epigenetic changes play a role in chronic pain conditions. Using reduced representation bisulfite sequencing (RRBS), we evaluated DNA methylation profiles of adults with non-specific cLBP (n = 50) and pain-free controls (n = 48). We identified 28,325 hypermethylated and 36,936 hypomethylated CpG sites (p < 0.05). After correcting for multiple testing, we identified 159 DMRs (q < 0.01and methylation difference > 10%), the majority of which were located in CpG island (50%) and promoter regions (48%) on the associated genes. The genes associated with the differentially methylated regions were highly enriched in biological processes that have previously been implicated in immune signaling, endochondral ossification, and G-protein coupled transmissions. Our findings support inflammatory alterations and the role of bone maturation in cLBP. This study suggests that epigenetic regulation has an important role in the pathophysiology of non-specific cLBP and a basis for future studies in biomarker development and targeted interventions.
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spelling pubmed-76585082020-11-20 Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain Aroke, Edwin N Overstreet, Demario S Penn, Terence M Crossman, David K Jackson, Pamela Tollefsbol, Trygve O Quinn, Tammie L Yi, Nengjun Goodin, Burel R Mol Pain Research Article Chronic low back pain (cLBP) that cannot be attributable to a specific pathoanatomical change is associated with high personal and societal costs. Still, the underlying mechanism that causes and sustains such a phenotype is largely unknown. Emerging evidence suggests that epigenetic changes play a role in chronic pain conditions. Using reduced representation bisulfite sequencing (RRBS), we evaluated DNA methylation profiles of adults with non-specific cLBP (n = 50) and pain-free controls (n = 48). We identified 28,325 hypermethylated and 36,936 hypomethylated CpG sites (p < 0.05). After correcting for multiple testing, we identified 159 DMRs (q < 0.01and methylation difference > 10%), the majority of which were located in CpG island (50%) and promoter regions (48%) on the associated genes. The genes associated with the differentially methylated regions were highly enriched in biological processes that have previously been implicated in immune signaling, endochondral ossification, and G-protein coupled transmissions. Our findings support inflammatory alterations and the role of bone maturation in cLBP. This study suggests that epigenetic regulation has an important role in the pathophysiology of non-specific cLBP and a basis for future studies in biomarker development and targeted interventions. SAGE Publications 2020-11-10 /pmc/articles/PMC7658508/ /pubmed/33169629 http://dx.doi.org/10.1177/1744806920972889 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Aroke, Edwin N
Overstreet, Demario S
Penn, Terence M
Crossman, David K
Jackson, Pamela
Tollefsbol, Trygve O
Quinn, Tammie L
Yi, Nengjun
Goodin, Burel R
Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain
title Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain
title_full Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain
title_fullStr Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain
title_full_unstemmed Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain
title_short Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain
title_sort identification of dna methylation associated enrichment pathways in adults with non-specific chronic low back pain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658508/
https://www.ncbi.nlm.nih.gov/pubmed/33169629
http://dx.doi.org/10.1177/1744806920972889
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