High Frequency of CF Transmembrane Conductance Regulator (CFTR) Mutations in a Population with Persistent Asthma and/or Chronic Rhinosinusitis

Meth, Marc J.; Serota, Martin; Rosenthal, David W.; Santiago, Maria; Cavuoto, M.A.

doi:10.1016/j.jaci.2008.12.598

Cited by 6 publications

(6 citation statements)

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“…A small retrospective US study of patients with CRS who underwent full sequencing of CFTR (n=68) found 38% of these patients had mutations in CFTR (n=26). 68 The prevalence of CFTR mutations was slightly higher in CRS patients with comorbid asthma (42%, or 16 out of 38 patients), and even higher in their very small sample of patients with CRSwNP (66%, or 4 out of 6 CRSwNP patients in the study). 68 The authors estimated they would have missed 75% of CFTR mutation carriers (i.e., 30 of 41 patients) if they had employed only genetic screening for the 23 most common CFTR mutations for CF patients of European ancestry.…”

Section: Genetics Of Crs: Current State Of the Field And Limitations mentioning

confidence: 67%

“…68 The prevalence of CFTR mutations was slightly higher in CRS patients with comorbid asthma (42%, or 16 out of 38 patients), and even higher in their very small sample of patients with CRSwNP (66%, or 4 out of 6 CRSwNP patients in the study). 68 The authors estimated they would have missed 75% of CFTR mutation carriers (i.e., 30 of 41 patients) if they had employed only genetic screening for the 23 most common CFTR mutations for CF patients of European ancestry. 68 As gene sequencing becomes a feasible and inexpensive method for investigation, applying this technology to further study of CFTR in CRS may prove worthwhile.…”

Section: Genetics Of Crs: Current State Of the Field And Limitations mentioning

confidence: 67%

“…68 The authors estimated they would have missed 75% of CFTR mutation carriers (i.e., 30 of 41 patients) if they had employed only genetic screening for the 23 most common CFTR mutations for CF patients of European ancestry. 68 As gene sequencing becomes a feasible and inexpensive method for investigation, applying this technology to further study of CFTR in CRS may prove worthwhile.…”

Section: Genetics Of Crs: Current State Of the Field And Limitations mentioning

confidence: 99%

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Genetics of chronic rhinosinusitis: State of the field and directions forward

Hsu

Avila

Kern

et al. 2013

Journal of Allergy and Clinical Immunology

107

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The etiology of chronic rhinosinusitis (CRS) remains unclear. Study of the genetic susceptibility to CRS may be a valuable strategy to understand the pathogenesis of this burdensome disorder. The purpose of this review is to critically evaluate the current literature regarding the genetics of CRS in a comprehensive fashion. The most promising findings from candidate gene studies include the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR), as well as genes involved in antigen presentation, innate and adaptive immune responses, tissue remodeling, and arachidonic acid metabolism. We also review the few hypothesis-independent genetic studies of CRS (i.e., linkage analysis and pooling-based genome-wide association studies). Interpretation of the current literature is limited by challenges with study design, sparse replication, few functional correlates of associated polymorphisms, and inadequate examination of linkage disequilibrium or expression quantitative trait loci for reported associations. Given the relationship of CRS to other airway disorders with well-characterized genetic components (e.g., asthma), study of the genetics of CRS deserves increased attention and investment, including the organization of large, detailed, and collaborative studies to advance knowledge of the mechanisms that underlie this disorder.

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Section: Genetics Of Crs: Current State Of the Field And Limitations mentioning

confidence: 67%

Section: Genetics Of Crs: Current State Of the Field And Limitations mentioning

confidence: 67%

Section: Genetics Of Crs: Current State Of the Field And Limitations mentioning

confidence: 99%

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Genetics of chronic rhinosinusitis: State of the field and directions forward

Hsu

Avila

Kern

et al. 2013

Journal of Allergy and Clinical Immunology

107

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“…In the context of these dramatic changes in mucus quantity and quality, the expansion and programming of tuft cells that enables production of PGE2 may serve to hydrate the mucus and promote clearance via CFTR. The specific importance of CFTR activity in maintaining fluid transport in the allergic airway is reinforced by the observation that CFTR gene mutations are found in patients with asthma or nasal polyps (without cystic fibrosis) at higher rates than healthy control populations (34). While PGE2-enhanced mucus transport may be beneficial in the context of pathological mucus production in the allergic airway, further studies are needed to define the full spectrum of PGE2 effects, as well as the function of other secreted factors derived from tuft cells.…”

Section: Discussionmentioning

confidence: 99%

IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function

Kotas

Moore

Gurrola

et al. 2022

Preprint

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Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which are largely attributed to the effects of IL-13 on common epithelial cell types (mucus secretory and ciliated cells). The role of rare cells in airway T2 inflammation is less clear, though tuft cells have been shown to be critical in the initiation of T2 immunity in the intestine. Using bulk and single cell RNA sequencing of airway epithelium and mouse modeling, we find that IL-13 expands and programs airway tuft cells towards eicosanoid metabolism, and that tuft cell deficiency leads to a reduction in airway prostaglandin E2 (PGE2) concentration. Allergic airway epithelia bear a signature of prostaglandin E2 activation, and PGE2 activation leads to CFTR-dependent ion and fluid secretion and accelerated mucociliary transport. Together these data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.

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“…There is currently no published GWAS performed only on patients with CRSwNP but there is a pooling-based GWAS done on patients with CRS (both CRSsNP and CRSwNP) [ 13 ] as well as several studies of candidate genes [ 14 ]. These studies have implicated several genes and pathways such as the cystic fibrosis transmembrane conductance regulator gene ( CFTR ) [ 15 , 16 ] and, among others, genes involved in immunity [ 17 – 20 ], inflammation [ 21 , 22 ], tissue remodelling [ 20 ] and arachidonic acid metabolism [ 23 ]…”

Section: Introductionmentioning

confidence: 99%

A family-based genome-wide association study of chronic rhinosinusitis with nasal polyps implicates several genes in the disease pathogenesis

et al. 2017

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BackgroundThe pathogenesis of chronic rhinosinusitis with nasal polyps is largely unknown. Previous studies have given valuable information about genetic variants associated with this disease but much is still unexplained. Our goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study.Methods427 patients (293 males and 134 females) with CRSwNP and 393 controls (175 males and 218 females) were recruited from several Swedish hospitals. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX). Analyses of pathway enrichment, gene expression levels and expression quantitative trait loci were then performed in turn.ResultsNone of the analysed SNPs reached genome wide significant association of 5.0 x 10−8. Pathway analyses using our top 1000 markers with the most significant association p-values resulted in 138 target genes. A comparison between our target genes and gene expression data from the NCBI Gene Expression Omnibus database showed significant overlap for 36 of these genes. Comparisons with data from expression quantitative trait loci showed the most skewed allelic distributions in cases with chronic rhinosinusitis with nasal polyps compared with controls for the genes HLCS, HLA-DRA, BICD2, VSIR and SLC5A1.ConclusionOur study indicates that HLCS, HLA-DRA, BICD2, VSIR and SLC5A1 could be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. HLA-DRA has been associated with chronic rhinosinusitis with nasal polyps in previous studies and HLCS, BICD2, VSIR and SLC5A1 may be new targets for future research.

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High Frequency of CF Transmembrane Conductance Regulator (CFTR) Mutations in a Population with Persistent Asthma and/or Chronic Rhinosinusitis

Cited by 6 publications

References 0 publications

Genetics of chronic rhinosinusitis: State of the field and directions forward

Genetics of chronic rhinosinusitis: State of the field and directions forward

IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function

A family-based genome-wide association study of chronic rhinosinusitis with nasal polyps implicates several genes in the disease pathogenesis

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