Trial reportThe Journal of clinical investigation2020
Decreased sphingolipid synthesis in children with 17q21 asthma-risk genotypes.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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.
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Who cites it
50 citing papers in PubMed, 68 citations in OpenAlex.
- Adjunctive Probiotics Alleviates Asthmatic Symptoms via Modulating the Gut Microbiome and Serum Metabolome.Microbiology spectrum · 2021Trial
- Type 2-low Asthma: Epidemiology, Multiomics, and Emerging Therapies.Current allergy and asthma reports · 2026Review
- A Multi-Omics Approach Uncovers Divergent Mechanisms of Asthma in Normal Weight and Obese Children.Metabolites · 2026Article
- Asthma endotypes and theratypes.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Article
- Beyond the Usual Suspects: Unmasking Low-T2 Asthma in Children.Journal of clinical medicine · 2026Review
- Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis.Journal of endocrinological investigation · 2025Article
- Independent association of a 17q21 variant with exacerbations in type 2-low adult asthma.The journal of allergy and clinical immunology. Global · 2025Article
- Improvement of glucocorticoid sensitivity and attenuation of pulmonary allergic reactions by exogenous supplementation with betaine in HDM and LPS-induced allergic mouse model.Clinical and translational allergy · 2025Article
- Possible Involvement of Lysophospholipids in Severe Asthma as Novel Lipid Mediators.Biomolecules · 2025Review
- Review
- Sex differences in asthma: omics evidence and future directions.Frontiers in genetics · 2025Review
- Association between nasopharyngeal airway lipidome signatures of infants with severe bronchiolitis and risk of recurrent wheeze: A prospective multicenter cohort study.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2024Article
- Heavy Metal Exposure-Mediated Dysregulation of Sphingolipid Metabolism.Antioxidants (Basel, Switzerland) · 2024Article
- Advances in non-type 2 severe asthma: from molecular insights to novel treatment strategies.The European respiratory journal · 2024Review
- Novel Role of the GSDMB/IFNG Axis in Childhood Asthma.American journal of respiratory and critical care medicine · 2024Article
- Sphingolipid classes and the interrelationship with pediatric asthma and asthma risk factors.Allergy · 2024Article
- A cross talk between microbial metabolites and host immunity: Its relevance for allergic diseases.Clinical and translational allergy · 2024Review
- New Therapeutic Options in Pulmonal Diseases: Sphingolipids and Modulation of Sphingolipid Metabolism.Handbook of experimental pharmacology · 2024Review
- Sphingolipids in Childhood Asthma and Obesity (SOAP Study): A Protocol of a Cross-Sectional Study.Metabolites · 2023Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Risk for childhood asthma is conferred by alleles within the 17q21 locus affecting ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) expression. ORMDL3 inhibits sphingolipid de novo synthesis. Although the effects of 17q21 genotypes on sphingolipid synthesis in human asthma remain unclear, both decreased sphingolipid synthesis and ORMDL3 overexpression are linked to airway hyperreactivity. To characterize the relationship of genetic asthma susceptibility with sphingolipid synthesis, we analyzed asthma-associated 17q21 genotypes (rs7216389, rs8076131, rs4065275, rs12603332, and rs8067378) in both children with asthma and those without asthma, quantified plasma and whole-blood sphingolipids, and assessed sphingolipid de novo synthesis in peripheral blood cells by measuring the incorporation of stable isotope-labeled serine (substrate) into sphinganine and sphinganine-1-phosphate. Whole-blood dihydroceramides and ceramides were decreased in subjects with the 17q21 asthma-risk alleles rs7216389 and rs8076131. Children with nonallergic asthma had lower dihydroceramides, ceramides, and sphingomyelins than did controls. Children with allergic asthma had higher dihydroceramides, ceramides, and sphingomyelins compared with children with nonallergic asthma. Additionally, de novo sphingolipid synthesis was lower in children with asthma compared with controls. These findings connect genetic 17q21 variations that are associated with asthma risk and higher ORMDL3 expression to lower sphingolipid synthesis in humans. Altered sphingolipid synthesis may therefore be a critical factor in asthma pathogenesis and may guide the development of future therapeutics.
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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.