ArticleHuman molecular genetics2015
Risk of childhood asthma is associated with CpG-site polymorphisms, regional DNA methylation and mRNA levels at the GSDMB/ORMDL3 locus.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- Decreased sphingolipid synthesis in children with 17q21 asthma-risk genotypes.The Journal of clinical investigation · 2020Trial
- Associations Between Genetic Variants in the 17q21 Locus,Children (Basel, Switzerland) · 2026Article
- Pathway-level epigenetic modeling illuminates the methylation architecture to asthma risk across tissues.Epigenetics & chromatin · 2026Article
- Estimating in silico causal effects of DNA methylation on gene expression through genetic anchors in airway epithelium in asthma.Science advances · 2026Article
- Article
- Bioinformatics analysis and qRT-PCR validation of iron metabolism-related genes in pediatric asthma.PloS one · 2026Article
- Exploring Potential Stress Granule-Related Biomarkers in Childhood Asthma Using Integrated Bioinformatics and Machine Learning.Journal of inflammation research · 2026Article
- Integrated multi-omics profiling reveals shared mechanistic pathways in asthma-allergic rhinitis comorbidity: A hybrid machine learning framework leveraging Mendelian randomization for precision diagnostics.The World Allergy Organization journal · 2025Article
- Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections.International journal of molecular sciences · 2025Review
- Suppression of regulatory factor X 7 alleviates airway remodeling and inflammation in childhood asthma.CytoJournal · 2025Article
- No longer married to inflammasome signaling: the diverse interacting pathways leading to pyroptotic cell death.The Biochemical journal · 2022Review
- Mechanistic Insights into Gasdermin Pore Formation and Regulation in Pyroptosis.Journal of molecular biology · 2022Review
- Epigenetic regulation of pediatric and neonatal immune responses.Pediatric research · 2022Review
- Sphingolipids and Asthma.Advances in experimental medicine and biology · 2022Article
- GSDMD-mediated pyroptosis: a critical mechanism of diabetic nephropathy.Expert reviews in molecular medicine · 2021Review
- Perinatal origins of chronic lung disease: mechanisms-prevention-therapy-sphingolipid metabolism and the genetic and perinatal origins of childhood asthma.Molecular and cellular pediatrics · 2021Review
- Association of Gasdermin B Gene GSDMB Polymorphisms with Risk of Allergic Diseases.Biochemical genetics · 2021Article
- DNA methylation and gene expression profiles to identify childhood atopic asthma associated genes.BMC pulmonary medicine · 2021Article
- High-resolution targeted bisulfite sequencing reveals blood cell type-specific DNA methylation patterns in IL13 and ORMDL3.Clinical epigenetics · 2021Observational
- Characteristics and Mechanisms of a Sphingolipid-associated Childhood Asthma Endotype.American journal of respiratory and critical care medicine · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Single-nucleotide polymorphisms (SNPs) in GSDMB (Gasdermin B) and ORMDL3 (ORMDL sphingolipid biosynthesis regulator 3) are strongly associated with childhood asthma, but the molecular alterations contributing to disease remain unknown. We investigated the effects of asthma-associated SNPs on DNA methylation and mRNA levels of GSDMB and ORMDL3. Genetic association between GSDMB/ORMDL3 and physician-diagnosed childhood asthma was confirmed in the Swedish birth-cohort BAMSE. CpG-site SNPs (rs7216389 and rs4065275) showed differences in DNA methylation depending on carrier status of the risk alleles, and were significantly associated with methylation levels in two CpG sites in the 5' UTR (untranslated region) of ORMDL3. In the Swedish Search study, we found significant differences in DNA methylation between asthmatics and controls in five CpG sites; after adjusting for lymphocyte and neutrophil cell counts, three remained significant: one in IKZF3 [IKAROS family zinc finger 3 (Aiolos); cg16293631] and two in the CpG island (CGI) of ORMDL3 (cg02305874 and cg16638648). Also, cg16293631 and cg02305874 correlated with mRNA levels of ORMDL3. The association between methylation and asthma was independent of the genotype in rs7216389, rs4065275 and rs12603332. Both SNPs and CpG sites showed significant associations with ORMDL3 mRNA levels. SNPs influenced expression independently of methylation, and the residual association between methylation and expression was not mediated by these SNPs. We found a differentially methylated region in the CGI shore of ORMDL3 with six CpG sites less methylated in CD8(+) T-cells. In summary, this study supports that there are differences in DNA methylation at this locus between asthmatics and controls; and both SNPs and CpG sites are independently associated with ORMDL3 expression.
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