ArticleThe Journal of clinical investigation2008
Complex two-gene modulation of lung disease severity in children with cystic fibrosis.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
65 citing papers in PubMed, 3 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review.Human mutation · 2024Pooled it
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.Nature communications · 2015Pooled it
- Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema.American journal of respiratory and critical care medicine · 2011Trial
- Article
- Reconsidering the Diagnosis: Abnormal Sweat Chloride Tests in Non-CF Bronchiectasis.Pediatric pulmonology · 2025Article
- From CFTR to a CF signalling network: a systems biology approach to study Cystic Fibrosis.BMC genomics · 2024Article
- Impact of intrinsic and extrinsic risk factors on early-onset lung disease in cystic fibrosis.Pediatric pulmonology · 2023Article
- Review
- Subversion of the Complement System by Pseudomonas aeruginosa.Journal of bacteriology · 2023Review
- Article
- Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells.Cell & bioscience · 2023Article
- Occurrence of Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Patients with Allergic Bronchopulmonary Aspergillosis Complicating Asthma.Mycopathologia · 2022Article
- Mucosal Immunity in Cystic Fibrosis.Journal of immunology (Baltimore, Md. : 1950) · 2021Review
- Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.Genes · 2021Review
- Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies.Pharmaceutics · 2020Review
- The Role of MicroRNA in the Airway Surface Liquid Homeostasis.International journal of molecular sciences · 2020Review
- The genetics and genomics of cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Review
- Applying whole-genome sequencing in relation to phenotype and outcomes in siblings with cystic fibrosis.Cold Spring Harbor molecular case studies · 2020Article
- Transforming Growth Factor-β1 Selectively Recruits microRNAs to the RNA-Induced Silencing Complex and Degrades CFTR mRNA under Permissive Conditions in Human Bronchial Epithelial Cells.International journal of molecular sciences · 2019Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-beta1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function.
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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.