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.

项目摘要 /摘要 慢性腰痛（CLBP）持续超过12周，与高货币相关（高达2000亿美元 每年在美国）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，降低生产率，污名，抑郁和加速衰老。美国个人 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 与其他种族群体相比，CLBP，尤其是高加索人/白人。这种差异强调了 黑人中CLBP的负担要高得多，这会因低社会经济地位而加剧， 污名和歧视。但是，与1）引起和 在CLBP中维持种族差异，2）这些因素对CLBP结果较差的相对贡献 黑人。遗传和环境因素会影响慢性疼痛。 DNA甲基化（DNAM）是一种 表观遗传机制，环境因素改变了哪些基因是转旋或关闭的，而没有 改变DNA序列。在我们的初步数据和文献中，我们提出了前瞻性的 从正在进行的父母研究（R01MD010441）中收集血液样本，以阐明引起的机制 并维持CLBP种族差异。我们的中心假设是黑人经历了更不利的 环境暴露于美国的白人，这可能会引起dnam的变化，从而导致和维持 黑人更严重和致命的CLBP。我们的主要目标是发现新颖的表观遗传和基因 CLBP种族差异的基础的表达机制。我们将使用尖端技术，减少 代表Bisulfite测序（RRB）和RNA序列（RNA-Seq），以确定DNAM和基因 表达变化。我们的具体目的是1）确定DNAM和Gene的种族群体差异 黑人和白人之间有和没有CLBP的表达，以及2）确定DNAM和GENE是否是 表达模式与压力大的环境暴露以及CLBP的严重程度有关。向我们 知识，没有研究检查心理，社会经济地位，表观基因组和转录组数据 在种族不同的CLBP的成年人样本中。结合父母研究中严格的社会心理数据， 通过这项辅助研究的分子信息，代表了种族差异研究的范式转移 在CLBP中。该项目很重要，因为它将增加我们对CLBP的理解，并可能为干预提供信息 研究逆转表观基因组学变化的研究，以推动CLBP成果，这将使所有人的生活质量更高 患有CLBP的患者。