表观遗传学研究机制，如DNA甲基化、组蛋白修饰、非编码RNA和替代多腺苷酸化，这些机制可以在不改变DNA碱基对结构的情况下修改基因活性。由于这些变化是可逆的，它们在开发新型治疗方法方面具有潜力。目前，美国食品和药物管理局（FDA）批准了七种针对表观遗传变化的药物，并在治疗某些癌症的商业上市。然而，在美国以前尚未进行关于慢性鼻窦炎（CRS）的表观遗传学研究。本研究的目标是调查CRS与对照组鼻窦DNA甲基化模式，以揭示对CRS受试者产生环境诱导的表观遗传变化。研究了CRS的筛状骨样品和无CRS对照组的下鼻甲粘膜组织样品。通过还原表示亚硫酸酯测序研究了DNA甲基化。使用RADMeth®生物统计软件包鉴定了CRS和对照组之间的差异甲基化区域（DMRs）。对DMRs进行了Ingenuity Pathway分析，以鉴定顶级上游调节因子和基因通路。共研究了64名CRS受试者（36名CRSwNP；28名CRSsNP）和29名对照组的93个样本。CRS和对照组样本在13,662个CpG位点和1381个DMRs上有差异。鉴定出的顶级上游调节因子包括：1. CRS与对照组：TGFB1、TNF、TP53、DGCR8和β-雌二醇。 2. CRSwNP与对照组：TGFB1、CTNNB1、脂多糖、ID2和TCF7L2。3.CRSsNP与对照组：MYOD1、丙酮、ID2、ST8SIA4和LEPR。鉴定出了对照组和CRS、CRSwNP和CRSsNP之间的甲基化模式差异。环境诱导的表观遗传变化似乎与新型炎症、免疫、重塑通路以及影响上皮完整性、细胞增殖、稳态、血管通透性以及其他尚未确定的通路和基因有关。

Epigenetics studies mechanisms such as DNA methylation, histone modifications, non-coding RNAs, and alternative polyadenylation that can modify gene activity without changing the underlying DNA nucleotide base-pair structure. Because these changes are reversible, they have potential in developing novel therapeutics. Currently, seven pharmaceutical agents targeting epigenetic changes are FDA approved and commercially available for treatment of certain cancers. However, studies investigating epigenetics in chronic rhinosinusitis (CRS) have not been undertaken previously in the United States.The goal of this study was to investigate sinonasal DNA methylation patterns in CRS versus controls, to discern environmentally-induced epigenetic changes impacting CRS subjects.Ethmoidal samples from CRS and inferior turbinate mucosal tissue samples from controls without CRS were studied. DNA methylation was studied by Reduced Representation Bisulfite Sequencing. RADMeth® biostatistical package was used to identify differentially methylated regions (DMRs) between CRS and controls. Ingenuity Pathway analysis of DMRs was performed to identify top upstream regulators and canonical pathways. Ninety-three samples from 64 CRS subjects (36 CRSwNP; 28 CRSsNP) and 29 controls were studied. CRS and control samples differed in 13 662 CpGs sites and 1381 DMRs. Top upstream regulators identified included: 1. CRS versus controls: TGFB1, TNF, TP53, DGCR8, and beta-estradiol. 2. CRSwNP versus controls: TGFB1, CTNNB1, lipopolysaccharide, ID2, and TCF7L2. 3. CRSsNP versus controls: MYOD1, acetone, ID2, ST8SIA4, and LEPR.Differential patterns of methylation were identified between controls and CRS, CRSwNP, and CRSsNP. Epigenetic, environmentally-induced changes related to novel, inflammatory, immunologic, and remodeling pathways appear to affect epithelial integrity, cell proliferation, homeostasis, vascular permeability, and other yet uncharacterized pathways and genes.