Genetics and Epigenetics of Nasal Polyposis: A Systematic Review

Abstract

Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses, often associated with nasal polyps (CRSwNP) in the most severe cases. Like other complex diseases, genetics are thought to play an important role in the risk and development of the disease, and the environment may also contribute to modulate the epigenetic signature in the patients. In the present systematic review, we aimed at compiling all the published data about genetic and epigenetic variations in CRSwNP since 2000. We found 104 articles, 24 of them related to epigenetic studies. From these articles, we have identified more than 150 genetic variants in 99 genes involved in NP pathogenesis that were clustered into eight main networks, linking genes involved in inflammation, immune response, such as MHC, cytokine genes, or TNF; leukotriene metabolism, and extracellular matrix. A total of 89 miRNAs have been also identified, basically associated with biological functions such as cell cycle, inflammation, and immune response. We have also proposed a potential relationship between identified miRNAs and genes that may open new lines of investigation. The in-depth knowledge of gene variants and epigenetic traits could contribute to design more tailored treatment for CRSwNP patients.

Genome-wide Epigenetic Study of Chronic Rhinosinusitis Tissues Reveals Dysregulated Inflammatory, Immunologic and Remodeling Pathways

“…3,4 Thus, without changing the genotype, epigenetic mechanisms change the individual's phenotype (observable characteristics and traits of an individual, including disease activity, severity, subtype that are determined by genotype and environmental factors). The common mechanisms involved in epigenetics are DNA methylation, histone modifications, non-coding RNAs 5,6 and alternative polyadenylation. 7 CpG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide.…”

Pre-asthma: a useful concept? A EUFOREA paper. Part 2—late onset eosinophilic asthma

“…These were clustered into 8 main networks, linking genes involved in inflammation and immune response (e.g., MHC), cytokine genes (e.g., TNF), leukotriene metabolism, and the extracellular matrix. Eighty-nine miRNAs were also identified, associated mainly with the cell cycle, inflammation, and the immune response ( 37 ).…”

TAS2R38 Bitter Taste Receptor Polymorphisms in Patients with Chronic Rhinosinusitis with Nasal Polyps Preliminary Data in Polish Population

“…Currently, the only fully proven genetic cause of CRS is a genetically determined ciliary impairment, as seen in patients with Kartagener's syndrome and primary ciliary dyskinesia (PCD), as well as nasal mucus dysfunction in cystic fibrosis (CF). Recent studies focusing on genetic and epigenetic aspects of nasal polyposis link this medical condition with genes involved in inflammation and immune response, cytokine genes, leukotriene metabolism, and the extracellular matrix [3]. Some of them have shown that abnormalities in the mobility and the activity of the ciliated epithelium of the upper respiratory tract may be related to the bitter taste receptors (T2Rs): TAS2R13, TAS2R19, TAS2R38, and TAS2R49 [4,5], out of which, TAS2R38 seems to have major significance [6][7][8][9].…”