Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
Clin Epigenetics. 2023 Feb 17;15(1):25. doi: 10.1186/s13148-023-01445-5.
Systemic sclerosis (SSc) is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects women and African Americans. Despite this, African Americans are dramatically underrepresented in SSc research. Additionally, monocytes show heightened activation in SSc and in African Americans relative to European Americans. In this study, we sought to investigate DNA methylation and gene expression patterns in classical monocytes in a health disparity population.
Classical monocytes (CD14+ + CD16-) were FACS-isolated from 34 self-reported African American women. Samples from 12 SSc patients and 12 healthy controls were hybridized on MethylationEPIC BeadChip array, while RNA-seq was performed on 16 SSc patients and 18 healthy controls. Analyses were computed to identify differentially methylated CpGs (DMCs), differentially expressed genes (DEGs), and CpGs associated with changes in gene expression (eQTM analysis).
We observed modest DNA methylation and gene expression differences between cases and controls. The genes harboring the top DMCs, the top DEGs, as well as the top eQTM loci were enriched for metabolic processes. Genes involved in immune processes and pathways showed a weak upregulation in the transcriptomic analysis. While many genes were newly identified, several other have been previously reported as differentially methylated or expressed in different blood cells from patients with SSc, supporting for their potential dysregulation in SSc.
While contrasting with results found in other blood cell types in largely European-descent groups, the results of this study support that variation in DNA methylation and gene expression exists among different cell types and individuals of different genetic, clinical, social, and environmental backgrounds. This finding supports the importance of including diverse, well-characterized patients to understand the different roles of DNA methylation and gene expression variability in the dysregulation of classical monocytes in diverse populations, which might help explaining the health disparities.
系统性硬化症（SSc）是一种多系统自身免疫性疾病，其病因尚不清楚， disproportionately 影响女性和非裔美国人。尽管如此，非裔美国人在 SSc 研究中严重代表性不足。此外，与欧洲裔美国人相比，单核细胞在 SSc 中以及非裔美国人中表现出更高的激活。在这项研究中，我们试图在健康差异人群中研究经典单核细胞中的 DNA 甲基化和基因表达模式。
从 34 名自我报告的非裔美国女性中通过 FACS 分离出经典单核细胞（CD14+ + CD16-）。从 12 名 SSc 患者和 12 名健康对照者的样本在 MethylationEPIC BeadChip 阵列上进行杂交，而 16 名 SSc 患者和 18 名健康对照者的 RNA-seq 进行。计算分析以鉴定差异甲基化 CpG（DMC）、差异表达基因（DEG）和与基因表达变化相关的 CpG（eQTM 分析）。
我们观察到病例和对照组之间的 DNA 甲基化和基因表达差异不大。含有顶级 DMC、顶级 DEG 以及顶级 eQTM 位点的基因富集了代谢过程。参与免疫过程和途径的基因在转录组分析中表现出微弱的上调。虽然许多基因是新发现的，但其他一些基因已在 SSc 患者的不同血细胞中被报道为差异甲基化或表达，支持它们在 SSc 中可能失调。
尽管与在主要为欧洲裔人群的其他血细胞类型中发现的结果形成对比，但这项研究的结果支持 DNA 甲基化和基因表达变异存在于不同细胞类型和不同遗传、临床、社会和环境背景的个体之间。这一发现支持了包括多样化、特征明确的患者的重要性，以了解不同人群中经典单核细胞的 DNA 甲基化和基因表达变异性在失调中的不同作用，这可能有助于解释健康差异。
