Genetics and epigenetics of chronic rhinosinusitis

Genomewide epigenetic study shows significant DNA hypermethylation in chronic rhinosinusitis versus control ethmoidal tissue

“…2 Previous genetic and epigenetic studies have implicated TNF alpha, showing higher levels in CRSwNP. 9 Other top URs include LPS (pro-inflammatory toxin on the outer membrane of gram-negative bacteria, activates TLR4 inflammation) and beta-estradiol (a sex hormone) both of which were identified in our previous study. 2 Overall, the results greatly overlap with our previous DNA methylation study which used ITM for control.…”

“…Accumulating evidence has shown the role of EMT in CRS 7,8 and is an interesting focus of current studies in CRS evolution. WNT/β‐catenin signaling, a key pathway identified in cancers, has been identified in other epigenetic studies in CRS 9 . HESCP is also implicated in cancers and pluripotent cells can differentiate into a wide variety of cells.…”

“…WNT/β-catenin signaling, a key pathway identified in cancers, has been identified in other epigenetic studies in CRS. 9 HESCP is also implicated in cancers and pluripotent cells can differentiate into a wide variety of cells. Additionally, we identified Th1 and Th2 activation pathway and Th2 pathway in CRS/CRSwNP versus controls, evidence that polyp status alone may not be an accurate marker to subclassify CRS.…”

“…TGFβ1 and SMAD3 emerged as one of the top URs in comparing CRS/CRSwNP with controls. TGFβ1 has been widely implicated in other genetic/epigenetic studies in CRS 9 . SMAD3 proteins influence TGFβ signaling, impacting cellular growth, proliferation, migration, and apoptosis.…”

Endotypic heterogeneity and pathogenesis in chronic rhinosinusitis

“…ECRS had upregulation of Charcot-Leyden crystal galectin (CLC), eotaxin-3, periostin (an extracellular matrix [ECM] protein), and cystatin SN (an inhibitor of cysteine proteases), indicating a T2 endotype. In contrast, NECRS presented upregulation of T1-related molecules (CXCL9, CXCL10, and CXCL11) and T3-related molecules (CXCL5 and CCL20) suggesting that the T1 and 3 endotype are frequently coexistent [8,9 ▪▪ ]. While multiple clusters (endotypes) have been recognized through clustering analysis using biomarkers in published studies, the prevailing consensus is that three primary endotypes (T1, T2, and T3), or sometimes two (T2 [eosinophilic] and non-T2 [mixed T1 and T3 or noneosinophilic]) exist.…”