ArticleThe Journal of allergy and clinical immunology2014
Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma.
Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Airway specific deregulation of asthma-related serpins impairs tracheal architecture and oxygenation in D. melanogaster.Scientific reports · 2024Article
- Exploring TSLP and IL-33 Serum Levels and Genetic Variants: Unveiling Their Limited Potential as Biomarkers for Mild Asthma in Children.Journal of clinical medicine · 2024Article
- Development and validation of a glycolysis-associated gene signature for predicting the prognosis, immune landscape, and drug sensitivity in bladder cancer.Frontiers in immunology · 2024Article
- Nasal TSLP and periostin in infants with severe bronchiolitis and risk of asthma at 4 years of age.Respiratory research · 2023Observational
- Nafamostat has anti-asthmatic effects associated with suppressed pro-inflammatory gene expression, eosinophil infiltration and airway hyperreactivity.Frontiers in immunology · 2023Article
- SPINK5 is a Prognostic Biomarker Associated With the Progression and Prognosis of Laryngeal Squamous Cell Carcinoma Identified by Weighted Gene Co-Expression Network Analysis.Evolutionary bioinformatics online · 2022Article
- The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development.Journal of asthma and allergy · 2022Review
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
- TSLP disease-associated genetic variants combined with airway TSLP expression influence asthma risk.The Journal of allergy and clinical immunology · 2022Article
- Second-hand smoke and NFE2L2 genotype interaction increases paediatric asthma risk and severity.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2021Article
- Article
- Building a Population Representative Pediatric Biobank: Lessons Learned From the Greater Cincinnati Childhood Cohort.Frontiers in public health · 2020Article
- Rhinovirus Attributes that Contribute to Asthma Development.Immunology and allergy clinics of North America · 2019Review
- A novel tumor suppressor SPINK5 targets Wnt/β-catenin signaling pathway in esophageal cancer.Cancer medicine · 2019Article
- Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci.The Journal of allergy and clinical immunology · 2018Article
- Expression and Regulation of Thymic Stromal Lymphopoietin and Thymic Stromal Lymphopoietin Receptor Heterocomplex in the Innate-Adaptive Immunity of Pediatric Asthma.International journal of molecular sciences · 2018Review
- The Innate Cytokines IL-25, IL-33, and TSLP Cooperate in the Induction of Type 2 Innate Lymphoid Cell Expansion and Mucous Metaplasia in Rhinovirus-Infected Immature Mice.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- TIPE2 Inhibits the Expression of Asthma-Related Inflammatory Factors in Hyperstretched Bronchial Epithelial Cells Through the Wnt/β-Catenin Pathway.Inflammation · 2017Article
- Phenotypic and genetic aspects of epithelial barrier function in asthmatic patients.The Journal of allergy and clinical immunology · 2017Review
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEpithelial genes have previously been associated with asthma but only explain a small fraction of heritability. In part, this might be due to epistasis, which is often not considered.
objectiveWe sought to determine independent and epistatic associations between filaggrin (FLG), serine protease inhibitor Kazal-type 5 (SPINK5), and thymic stromal lymphopoietin (TSLP) gene variants and childhood asthma.
methodsUsing a candidate gene approach, we genotyped 29 variants in FLG, SPINK5, and TSLP in asthmatic, allergic, and nonallergic nonasthmatic white and black children participating in the well-phenotyped Greater Cincinnati Pediatric Clinic Repository. Associations with asthma were also assessed in 6 replication populations.
resultsWe observed independent associations of variants in SPINK5 (P = .003) and TSLP (P = .006) with childhood asthma; a SPINK5 single nucleotide polymorphism was replicated. In subjects with 1 or more SPINK5 risk alleles, the absence of the TSLP protective minor alleles was associated with a significant increase in asthma (67% vs 53%, P = .0017). In contrast, the presence or absence of TSLP minor alleles did not affect asthma risk in subjects without the SPINK5 risk alleles. The SPINK5 and TSLP epistasis was replicated in a black population (P = .036) who did not display independent association with variants in these genes.
conclusionsOur results support epistasis between SPINK5 and TSLP, which contributes to childhood asthma. These findings emphasize the importance of using biology to inform analyses to identify genetic susceptibility to complex diseases. The results from our study have clinical relevance and support that the therapeutic effects of anti-TSLP therapy in asthmatic patients might be dependent on SPINK5 genotype.
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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.