Epigenomic and Gene Expression Signatures of Racial Differences in Chronic Low Back Pain

慢性腰痛种族差异的表观基因组和基因表达特征

• 批准号: 10612025
• 负责人: Edwin Ngomueh Aroke
• 金额: $ 37.3万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612025
• 关键词: Acceleration; Address; Adult; Affect; African American; Aging; Ancillary Study; Black Populations; Black race; Blood specimen; Brain-Derived Neurotrophic Factor; Caucasians; Chronic; Chronic low back pain; Clinical; Collagen; Cysteine; DNA; DNA Methylation; DNA Sequence; Data; Development; Discrimination; Disparity; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Fibromyalgia; Fostering; Foundations; Gene Expression; Gene Expression Profile; Genes; Genetic; Heritability; Hypermethylation; IFNGR2 gene; IL17C gene; Immune Response Genes; Individual; Inflammation; Interleukin-10; Intervention; Intervention Studies; Knowledge; Literature; Low Back Pain; Measures; Mental Depression; Methylation; Molecular; Moods; NFKB2 gene; NR3C2 gene; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Opioid Receptor; Pain; Pain Free; Parents; Participant; Patients; Persons; Pilot Projects; Postoperative Pain; Productivity; Promoter Regions; Protein Secretion; Proteins; Public Health; Quality of life; RUNX1 gene; Race; Research; Sampling; Severities; Socioeconomic Status; Spinal Fusion; Stress; Stressful Event; TNF gene; Technology; Tissue-Specific Gene Expression; Work; biomarker development; bisulfite sequencing; bone; calcification; chronic pain; chronic painful condition; cost; disability; epigenome; epigenomics; experience; improved outcome; innovation; insight; intervertebral disk degeneration; low socioeconomic status; methylation pattern; novel; pain outcome; peripheral blood; programs; prospective; psychologic; psychosocial; racial difference; racial discrimination; racial disparity; racial diversity; racial minority; racial population; receptor expression; response; social; social stigma; transcriptome sequencing; transcriptomics

PROJECT SUMMARY / ABSTRACT Chronic low back pain (cLBP), lasting more than 12 weeks, is associated with high monetary (up to $200 billion annually in the USA) and non-monetary societal and personal costs such as decreased quality of life, lowered self-worth, reduced productivity, stigma, depression, and accelerated aging. Individuals in the USA who identify with an African American/Black racial background experience more frequent, severe, and disabling cLBP compared to other racial groups, particularly Caucasians/Whites. This difference underscores the substantially higher burden of cLBP among Blacks, which are exacerbated by low socioeconomic status, stigma, and discrimination. However, there is a gap in knowledge relating to 1) the mechanisms that cause and sustain racial differences in cLBP, and 2) the relative contributions of these factors for worse cLBP outcomes in Blacks. Genetic and environmental factors influence chronic pain. DNA methylation (DNAm) is a type of epigenetic mechanism by which environmental factors alter which genes are turned-on or turned-off without changing the DNA sequence. Informed by our preliminary data and literature, we propose to prospectively collect blood samples from an ongoing parent study (R01MD010441) to elucidate the mechanism that causes and sustains racial differences in cLBP. Our central hypothesis is that Blacks experience more adverse environmental exposures than Whites in the USA, which may induce DNAm changes that cause and sustain more severe and disabling cLBP for Blacks. Our primary objective is to uncover novel epigenetic and gene expression mechanisms that underlie racial differences in cLBP. We will use cutting edge technology, reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), to determine DNAm and gene expression changes. Our specific aims are 1) to determine racial group differences in DNAm and gene expression between Blacks and Whites with and without cLBP, and 2) to determine if DNAm and gene expression patterns are associated with stressful environmental exposures as well as severity of cLBP. To our knowledge, no study has examined psychological, socioeconomic status, epigenomic, and transcriptomic data in a racially diverse sample of adults with cLBP. Combining rigorous psychosocial data from the parent study, with molecular information from this ancillary study, represents a paradigm shift in studies of racial differences in cLBP. This project is significant, as it will increase our understanding of cLBP and may inform intervention studies to reverse epigenomic changes that drive cLBP outcomes, which will allow a better quality of life for all patients with cLBP.

项目概要/摘要 持续超过 12 周的慢性腰痛 (cLBP) 与高额金钱（高达 2000 亿美元）相关。 在美国每年）以及非货币社会和个人成本，例如生活质量下降、降低 自我价值、生产力下降、耻辱、抑郁和加速衰老。在美国的个人 认同非裔美国人/黑人种族背景的经历更加频繁、严重和残疾 cLBP 与其他种族群体（特别是白种人/白人）的比较。这种差异强调了 黑人的 cLBP 负担显着增加，而社会经济地位低下又加剧了这一负担， 耻辱和歧视。然而，在以下方面存在知识空白：1）导致和 维持 cLBP 的种族差异，以及 2) 这些因素对 cLBP 结局较差的相对贡献 黑人。遗传和环境因素影响慢性疼痛。 DNA 甲基化 (DNAm) 是一种 环境因素通过表观遗传机制改变哪些基因被打开或关闭，而无需 改变DNA序列。根据我们的初步数据和文献，我们建议前瞻性地 从正在进行的母体研究 (R01MD010441) 中收集血液样本，以阐明导致 并维持 cLBP 的种族差异。我们的中心假设是黑人经历更多不利的事情 环境暴露程度高于美国白人，这可能会引起 DNAm 变化，从而导致和维持 对于黑人来说，cLBP 更为严重且致残。我们的主要目标是发现新的表观遗传学和基因 cLBP 种族差异背后的表达机制。我们将利用尖端技术，减少 代表性亚硫酸氢盐测序 (RRBS) 和 RNA 测序 (RNA-Seq)，以确定 DNAm 和基因 表情发生变化。我们的具体目标是 1) 确定 DNAm 和基因的种族群体差异 具有和不具有 cLBP 的黑人和白人之间的表达，以及 2) 确定 DNAm 和基因是否 表达模式与压力环境暴露以及 cLBP 的严重程度相关。致我们的 知识，没有研究检查心理、社会经济状况、表观基因组和转录组数据 在不同种族的 cLBP 成人样本中。结合家长研究中严格的心理社会数据， 借助这项辅助研究的分子信息，代表了种族差异研究的范式转变 在 cLBP 中。这个项目意义重大，因为它将增加我们对 cLBP 的理解，并可能为干预提供信息 逆转导致 cLBP 结果的表观基因组变化的研究，这将为所有人带来更好的生活质量 cLBP 患者。