ArticlePloS one2015
Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- A Systematic Review and Meta-Analysis of the Efficacy of Antimicrobial Chemoprophylaxis for Recurrent Acute Otitis Media in Children.Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery · 2025Pooled it
- Dysregulation of immune response in otitis media.Expert reviews in molecular medicine · 2021Pooled it
- Systems perspectives on pediatric otitis media: environmental exposures, genetic susceptibility, and biomarker-guided interventions.Frontiers in pediatrics · 2026Review
- Pattern recognition receptor signaling in otitis media: immune crosstalk and pathogenic mechanisms.Frontiers in immunology · 2026Review
- Determinants of Acute Otitis Media in Children: A Case-Control Study in West Java, Indonesia.Medicina (Kaunas, Lithuania) · 2025Article
- Surfactant proteins and innate immunity of otitis media.Innate immunity · 2022Review
- Toll-Like Receptors: Expression and Roles in Otitis Media.International journal of molecular sciences · 2021Review
- Risk factors for acute otitis media in primary school children: a case-control study in Central Java, Indonesia.Journal of public health research · 2021Article
- Innate Immunity in the Middle Ear Mucosa.Frontiers in cellular and infection microbiology · 2021Review
- Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification.Frontiers in immunology · 2021Review
- Immunologic dysfunction contributes to the otitis prone condition.The Journal of infection · 2020Review
- Panel 2- recent advance in otitis media bioinformatics.International journal of pediatric otorhinolaryngology · 2020Review
- Panel 8: Vaccines and immunology.International journal of pediatric otorhinolaryngology · 2020Review
- Genomics of Otitis Media (OM): Molecular Genetics Approaches to Characterize Disease Pathophysiology.Frontiers in genetics · 2020Review
- Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders.Frontiers in medicine · 2020Article
- Transcript Analysis Reveals a Hypoxic Inflammatory Environment in Human Chronic Otitis Media With Effusion.Frontiers in genetics · 2019Article
- Current Understanding of Host Genetics of Otitis Media.Frontiers in genetics · 2019Review
- Recent Perspectives on Gene-Microbe Interactions Determining Predisposition to Otitis Media.Frontiers in genetics · 2019Review
- Fisetin administration improves LPS-induced acute otitis media in mouse in vivo.International journal of molecular medicine · 2018Article
- Understanding the aetiology and resolution of chronic otitis media from animal and human studies.Disease models & mechanisms · 2017Review
Corrections and comments
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Authors and funding
18 authors at 9 institutions in 4 countries.
Funding
Abstract
backgroundPredisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts.
methodsWe investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls.
resultsIn the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFα secretion in myeloid dendritic cells.
conclusionsThe TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.
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