PMID- 35243180 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240210 IS - 2452-073X (Electronic) IS - 2452-073X (Linking) VI - 11 DP - 2022 Jan-Jul TI - Differential DNA methylation in Black and White individuals with chronic low back pain enrich different genomic pathways. PG - 100086 LID - 10.1016/j.ynpai.2022.100086 [doi] LID - 100086 AB - Compared to Non-Hispanic Whites (NHWs), individuals who self-identify as Non-Hispanic Blacks (NHBs) in the United States experience more severe and disabling chronic low back pain (cLBP). We hypothesized that differences in DNA methylation (DNAm) play a role in racial disparities in cLBP. PURPOSE: To determine the relationship between DNAm levels and racial group differences in adults with cLBP. Our study's secondary purpose was to perform a race-stratified comparison of adults with cLBP and pain-free controls and identify functional genomic pathways enriched by annotated differentially methylated genes. PATIENTS AND METHODS: We recruited 49 NHBs and 49 NHWs (49 cLBP and 49 pain-free controls, PFCs), analyzed DNAm from whole blood using reduced representation bisulfite sequencing, and identified enriched genomic pathways. RESULTS: Among participants with cLBP, we identified 2873 differentially methylated loci (DML; methylation differences of at least 10% and p < 0.0001), many of which were annotated to genes of importance to pain pathology. These DMLs significantly enriched pathways to involved in nociception/pain processing (Dopamine-DARPP32 Feedback in cAMP signaling, GABA Receptor Signaling, Opioid Signaling) and neuronal differentiation (e.g., Calcium Signaling, Axon Guidance Signaling, and Endocannabinoid Neuronal Synapse). Our race stratified analyses of individuals with cLBP versus PFCs revealed 2356 DMLs in NHBs and 772 DMLs in NHWs with p < 0.0001 and > 10% methylation difference. Ingenuity Pathway Analysis revealed that many pathways of significance to pain such as Corticotropin Releasing Hormone Signaling, White Adipose Tissue Browning, and GABA Receptor Signaling pathways, were more significant in NHBs than NHWs. CONCLUSION: Even though an individual's self-identified race is a social construct, not a biological variable, racism associated with that classification affects virtually every aspect of life, including disease risk. DNAm induced alterations in stress signaling pathways may explain worse pain outcomes in NHBs. CI - (c) 2022 The Author(s). FAU - Aroke, Edwin N AU - Aroke EN AD - School of Nursing, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Jackson, Pamela AU - Jackson P AD - School of Nursing, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Meng, Lingsong AU - Meng L AD - Department of Biostatistics, University of Florida, Gainesville, FL, USA. FAU - Huo, Zhiguang AU - Huo Z AD - Department of Biostatistics, University of Florida, Gainesville, FL, USA. FAU - Overstreet, Demario S AU - Overstreet DS AD - Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Penn, Terence M AU - Penn TM AD - Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Quinn, Tammie L AU - Quinn TL AD - Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Cruz-Almeida, Yenisel AU - Cruz-Almeida Y AD - College of Dentistry, University of Florida, Gainesville, FL, USA. AD - Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA. FAU - Goodin, Burel R AU - Goodin BR AD - Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA. LA - eng GR - P30 AG028740/AG/NIA NIH HHS/United States GR - R01 AR079178/AR/NIAMS NIH HHS/United States GR - R01 MD010441/MD/NIMHD NIH HHS/United States GR - T32 HS013852/HS/AHRQ HHS/United States PT - Journal Article DEP - 20220225 PL - United States TA - Neurobiol Pain JT - Neurobiology of pain (Cambridge, Mass.) JID - 101705141 PMC - PMC8885563 OTO - NOTNLM OT - Chronic low back pain OT - DML, DIfferentially methylated loci OT - DNA methylation OT - DNAm, DNA methylation OT - Epigenetics OT - NHB, Non-Hispanic Black OT - NHW, Non-Hispanic White OT - Non-specific chronic low back pain OT - PFC, Pain free control OT - Pain mechanisms OT - RRBS OT - RRBS, Reduced representation bisulfite sequencing OT - Racial pain disparities OT - cLBP, Chronic low back pain COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/03/05 06:00 MHDA- 2022/03/05 06:01 PMCR- 2022/02/25 CRDT- 2022/03/04 05:43 PHST- 2022/01/10 00:00 [received] PHST- 2022/02/07 00:00 [revised] PHST- 2022/02/20 00:00 [accepted] PHST- 2022/03/04 05:43 [entrez] PHST- 2022/03/05 06:00 [pubmed] PHST- 2022/03/05 06:01 [medline] PHST- 2022/02/25 00:00 [pmc-release] AID - S2452-073X(22)00003-4 [pii] AID - 100086 [pii] AID - 10.1016/j.ynpai.2022.100086 [doi] PST - epublish SO - Neurobiol Pain. 2022 Feb 25;11:100086. doi: 10.1016/j.ynpai.2022.100086. eCollection 2022 Jan-Jul.