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Updated: Jun 7, 2026
05:31
Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Upper airway microbiome interacts with GSDMB and ORMDL3 asthma risk SNPs to influence early-life wheeze risk.
Holly M Steininger1, Kathryn E McCauley1, Gabe E Braga1
1Benioff Center for Microbiome Medicine, Department of Medicine, University of California, San Francisco, Calif.
The Journal of Allergy and Clinical Immunology
|June 5, 2026
Summary
Genetic variants in the 17q12-q21 region and early-life nasal microbiota interact to influence childhood wheeze risk. Interventions targeting airway bacteria may help genetically susceptible children.
Area of Science:
- Genetics and Microbiology
- Pediatric Asthma Research
Background:
- Single-nucleotide polymorphisms (SNPs) in the chromosome 17q12-q21 region are associated with increased risk of chronic wheeze and asthma.
- Early-life nasal microbiota composition, particularly dominance by Moraxella, Streptococcus, or Haemophilus, independently increases wheeze and asthma risk.
Purpose of the Study:
- To investigate the interaction between 17q12-q21 risk SNPs and early-life nasal microbiota.
- To determine if this interaction modulates the risk of childhood wheeze.
Main Methods:
- Analysis of nasal microbiota composition using 16S rRNA sequencing in infants from two birth cohorts (COAST and URECA).
- Genotyping of nine 17q12-q21 risk SNPs from infant blood samples.
- Logistic regression to assess interactions between SNPs and microbiota types (MSH or CDSB) on wheeze risk.
- RNA sequencing of A549 lung epithelial cells with different rs7216389 genotypes.
Main Results:
- Specific SNPs in the ORM3 (rs8076131) and Gasdermin B (rs2305480, rs7216389) genes interacted with Moraxella, Streptococcus, or Haemophilus (MSH) dominated microbiota to increase early-life wheeze risk.
- Interactions with Corynebacterium, Dolosigranulum, Staphylococcus, or Bacillus (CDSB) microbiota reduced wheeze risk.
- A549 cells with the rs7216389 risk genotype showed reduced antimicrobial gene expression and increased microbial adherence.
Conclusions:
- Upper airway microbiota composition interacts with genetic variants at the 17q12-q21 locus to influence early-life wheeze risk.
- Genes involved in sphingolipid metabolism and intracellular antimicrobial responses are implicated in this interaction.
- Targeting pathogenic bacterial colonization may reduce wheeze in genetically susceptible children.
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