ArticleHuman genetics2006
The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis.
Article in Human genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review.Human mutation · 2024Pooled it
- Reconsidering the Diagnosis: Abnormal Sweat Chloride Tests in Non-CF Bronchiectasis.Pediatric pulmonology · 2025Article
- Genetic Modifying Factors of Cystic Fibrosis Phenotype: A Challenge for Modern Medicine.Journal of clinical medicine · 2021Review
- Article
- Association of cystic fibrosis transmembrane conductance regulator with epithelial sodium channel subunits carrying Liddle's syndrome mutations.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.Genes · 2021Review
- Genetic information from discordant sibling pairs points to ESRP2 as a candidate trans-acting regulator of the CF modifier gene SCNN1B.Scientific reports · 2020Article
- The Epithelial Sodium Channel Is a Modifier of the Long-Term Nonprogressive Phenotype Associated with F508del CFTR Mutations.American journal of respiratory cell and molecular biology · 2017Article
- The Contribution of the Airway Epithelial Cell to Host Defense.Mediators of inflammation · 2015Review
- Custom 4-Plex DiLeu Isobaric Labels Enable Relative Quantification of Urinary Proteins in Men with Lower Urinary Tract Symptoms (LUTS).PloS one · 2015Article
- Disease-modifying genes and monogenic disorders: experience in cystic fibrosis.The application of clinical genetics · 2014Review
- Clinical and molecular characterization of the potential CF disease modifier syntaxin 1A.European journal of human genetics : EJHG · 2013Article
- Genetic influences on cystic fibrosis lung disease severity.Frontiers in pharmacology · 2013Article
- Initial interrogation, confirmation and fine mapping of modifying genes: STAT3, IL1B and IFNGR1 determine cystic fibrosis disease manifestation.European journal of human genetics : EJHG · 2011Article
- An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion.BMC medical genetics · 2011Article
- Genes that determine immunology and inflammation modify the basic defect of impaired ion conductance in cystic fibrosis epithelia.Journal of medical genetics · 2011Article
- Article
- Differential decay of parent-of-origin-specific genomic sharing in cystic fibrosis-affected sib pairs maps a paternally imprinted locus to 7q34.European journal of human genetics : EJHG · 2010Article
- A mutation of the epithelial sodium channel associated with atypical cystic fibrosis increases channel open probability and reduces Na+ self inhibition.The Journal of physiology · 2010Article
- The NF-kappaB signaling in cystic fibrosis lung disease: pathophysiology and therapeutic potential.Discovery medicine · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CFTR mutations in cystic fibrosis (CF) lead to ion transport anomalities which predispose to chronic infection and inflammation of CF airways as the major determinants for morbidity and mortality in CF. Discordant clinical phenotypes of siblings with identical CFTR mutations and the large variability of clinical manifestations of patients who are homozygous for the most common mutation F508del suggest that both environment and genes other than CFTR contribute substantially to CF disease. The prime candidates for genetic modifiers in CF are elements of host defence such as the TNFalpha receptor and of ion transport such as the amiloride-sensitive epithelial sodium channel ENaC, both of which are encoded side by side on 12p13 (TNFRSF1A, SCNN1A) and 16p12 (SCNN1B, SCNN1G). Thirty-seven families with F508del-CFTR homozygous siblings exhibiting extreme clinical phenotypes that had been selected from the 467 pairs of the European CF Twin and Sibling Study were genotyped at 12p13 and 16p12 markers. The ENaC was identified as a modulator of CF by transmission disequilibrium at SCNN1G and association with CF phenotype intrapair discordance at SCNN1B. Family-based and case-control analyses and sequencing of SCNN1A and TNFRSF1A uncovered an association of the TNFRSF1A intron 1 haplotype with disease severity. Carriers of risk haplotypes were underrepresented suggesting a strong impact of both loci on survival. The finding that TNFRSF1A, SCNN1B and SCNN1G are clinically relevant modulators of CF disease supports current concepts that the depletion of airway surface liquid and inadequate host inflammatory responses trigger pulmonary disease in CF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.