Genetic Variants and Immune Responses in Asthma

Asthma is a heterogeneous chronic airway disorder driven by complex interactions between genetic predisposition and immune dysregulation. Variants in genes governing innate immune receptors, cytokine signalling and oxidative stress pathways shape individual susceptibility and disease course. Innate sensors such as toll-like receptors (TLRs) recognise environmental triggers and instruct downstream adaptive responses characterised by T helper 2 (Th2) cytokine profiles, immunoglobulin E (IgE) production and eosinophilic inflammation. Polymorphisms in genes regulating cytokine antagonists, antioxidant enzymes and pattern-recognition receptors influence the magnitude of airway hyperresponsiveness, remodelling and exacerbation risk. Genome-wide association scans have identified loci in IL-33, IL-1 family members, ORMDL3 and 17q21 region that modulate epithelial barrier function and mucosal immunity. Candidate gene studies of glutathione S-transferase (GST) isoforms highlight the role of impaired detoxification in pollutant-driven oxidative injury. Epigenetic modifications and microRNA networks further refine gene–environment interactions, pointing towards endotypes defined by distinct molecular pathways. Integration of genetic profiling with immunophenotyping offers promise for stratified prevention and targeted biotherapy in diverse populations.

Research from Nature Portfolio

Recent studies have explored how innate pattern-recognition receptors influence post-viral risk of asthma. One investigation of children hospitalised for infant bronchiolitis revealed that a variant in the TLR10 gene was associated with a four-fold increase in asthma prevalence by preschool age, demonstrating that loss-of-function polymorphisms in microbial sensors may sustain airway inflammation. Another report focused on TLR9 polymorphism in the same cohort, showing that infants carrying the TLR9 variant genotype were more likely to experience recurrent wheezing, suggesting a critical role for endosomal DNA sensors in shaping long-term airway reactivity. Together, these findings underscore how genetic variants in TLR subfamilies modulate innate immune thresholds and predispose to Th2-skewed responses in early life.

Genetic Variants and Immune Responses in Asthma publication trend

The graph below shows the total number of articles in genetic variants and immune responses in asthma across all publications each year (not limited to Nature Index journals).

Technical terms

Single nucleotide polymorphism (SNP): A variation at a single base pair in the DNA sequence that may affect gene function or regulation.

Toll-like receptor (TLR): An innate immune receptor that recognises conserved microbial or danger signals and initiates inflammatory responses.

Immunoglobulin E (IgE): A class of antibody involved in allergic responses and parasite defence, central to Th2-mediated asthma phenotypes.

Glutathione S-transferase P1 (GSTP1): An enzyme that detoxifies reactive oxygen species and electrophilic compounds, influencing oxidative stress in the lung.

Interleukin-1 receptor antagonist (IL-1RA): A natural inhibitor of interleukin-1 signalling that modulates pro-inflammatory cytokine activity in the airway.

References

1. Polymorphism in the gene encoding toll-like receptor 10 may be associated with asthma after bronchiolitis. Scientific Reports (2017).
2. Post-bronchiolitis wheezing is associated with toll-like receptor 9 rs187084 gene polymorphism. Scientific Reports (2016).
3. Association between Polymorphism of Interleukin‐1beta and Interleukin‐1 Receptor Antagonist Gene and Asthma Risk: A Meta‐Analysis. The Scientific World JOURNAL (2015).
4. Modification of additive effect between vitamins and ETS on childhood asthma risk according to GSTP1 polymorphism : a cross -sectional study. BMC Pulmonary Medicine (2015).
5. Traffic-Related Air Pollution, Oxidative Stress Genes, and Asthma (ECHRS). Environmental Health Perspectives (2009).