Differential DNA methylation in Black and White individuals with chronic low back pain enrich different genomic pathways

Edwin N Aroke; Pamela Jackson; Lingsong Meng; Zhiguang Huo; Demario S Overstreet; Terence M Penn; Tammie L Quinn; Yenisel Cruz-Almeida; Burel R Goodin

doi:10.1016/j.ynpai.2022.100086

Differential DNA methylation in Black and White individuals with chronic low back pain enrich different genomic pathways

Neurobiol Pain. 2022 Feb 25:11:100086. doi: 10.1016/j.ynpai.2022.100086. eCollection 2022 Jan-Jul.

Authors

Edwin N Aroke¹, Pamela Jackson¹, Lingsong Meng², Zhiguang Huo², Demario S Overstreet³, Terence M Penn³, Tammie L Quinn³, Yenisel Cruz-Almeida^{4

5}, Burel R Goodin³

Affiliations

¹ School of Nursing, University of Alabama at Birmingham, Birmingham, AL, USA.
² Department of Biostatistics, University of Florida, Gainesville, FL, USA.
³ Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴ College of Dentistry, University of Florida, Gainesville, FL, USA.
⁵ Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.

Abstract

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.

Keywords: Chronic low back pain; DML, DIfferentially methylated loci; DNA methylation; DNAm, DNA methylation; Epigenetics; NHB, Non-Hispanic Black; NHW, Non-Hispanic White; Non-specific chronic low back pain; PFC, Pain free control; Pain mechanisms; RRBS; RRBS, Reduced representation bisulfite sequencing; Racial pain disparities; cLBP, Chronic low back pain.

Abstract

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