RESUMO
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.
Assuntos
COVID-19 , Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/complicações , Rinite/genética , Rinite/metabolismo , Pólipos Nasais/complicações , Pólipos Nasais/genética , Pólipos Nasais/metabolismo , Transcriptoma , Cílios/metabolismo , COVID-19/complicações , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2/genética , Mucosa Nasal/metabolismo , Sinusite/complicações , Sinusite/genética , Sinusite/metabolismo , Doença Crônica , Proteínas de Membrana Transportadoras/metabolismoRESUMO
OBJECTIVES: We performed a systematic review on single-nucleotide polymorphisms and risk-related chronic rhinosinusitis. DESIGN AND SETTING: A comprehensive review of the last 20 years' English language literature regarding chronic rhinosinusitis and single-nucleotide polymorphisms was performed. We included in the synthesis all the papers reporting gene variation implicated in the pathogenesis of chronic inflammation and polyps. RESULTS: We found 12 papers with 9127 patients, of which 2739 CRS cases and 6388 controls. The major comorbidities reported related to chronic rhinosinusitis were atopy in 4555 (49.9%), asthma in 4594 (50.33%), Samter Triad in 448 (4.9%) and eosinophilia in 391 subjects (4.28%). CONCLUSION: Our systematic review revealed the major SNPs significantly associated with chronic rhinosinusitis and the specific pathways involved. Given the presence of different extraction methods and samples sequencing, further studies with larger courts are necessary to identify significative single-nucleotide polymorphisms.