Figures (0)  Tables (3)
    • Gene symbol Gene function Association with asthma pathogenesis Etiology of genetic variations
      ORAI1[11] Calcium ion regulation, T-cell activation, cytokine production. Variants linked to increased asthma susceptibility; especially, related to the immune response to allergens. Genetic mutations and allergens can influence its expression and immune response.
      IL4[12,13] Promotes differentiation of T-helper cells, leading to Th2-mediated inflammation IL4 drives IgE production and allergic responses, contributing to asthma; especially, allergic asthma. Genetic mutations and environmental allergens like pollen and dust mites increase IL4 expression.
      ADAM33[14] Involved in airway remodeling and smooth muscle regulation Contribute to airway hyperresponsiveness and remodeling features of asthma. Genetic changes; tobacco smoke and air pollution can trigger ADAM33 activation.
      GSTM1[15−17] Detoxifies harmful substances like environmental pollutants GSTM1 gene deletion is associated with asthma risk; especially, in children exposed to pollution. Genetic deletion of GSTM1 and environmental pollutants (e.g. tobacco smoke).
      FLG (Filaggrin)[18,19] Maintains skin integrity and prevents allergens entering to the body FLG mutations are linked to asthma; especially, in children with eczema, due to a weakened skin barrier. Genetic mutations; allergens or irritants like harsh chemicals and pollution.
      GATA3[20,21] Transcription factor regulating Th2 differentiation. GATA3 variants are associated with allergic asthma and Th2-mediated inflammation. Genetic variants; and environmental allergens contribute to GATA3 overexpression.
      STAT6[22] Transcription factor helps in Th2 differentiation and cytokine production in allergic responses. Variants increase susceptibility to asthma, especially in children with allergic tendencies. Genetic variants; and environmental allergens like pollen can promote STAT6 activation.
      TNF[23] Pro-inflammatory cytokine, immune activation & airway inflammation. Variants linked to asthma, particularly through increased airway inflammation and tissue remodeling. Genetic mutations; air pollution and allergens exacerbate TNF expression.
      CD14[24,25] Receptor activates immune responses to environmental triggers, such as bacteria and allergens. Variants in CD14 are associated with asthma, particularly in children exposed to environmental allergens. Genetic changes; and environmental exposures (e.g., dust mites, mold) increase CD14-mediated immune activation.
      IKZF3[26,27] Regulates immune cell differentiation and activation. Contribute to asthma susceptibility, influencing immune responses. Genetic predisposition; environmental allergens.
      MUC5AC[28] Secreted protein involved in mucus production in the airways. Overexpression of MUC5AC is associated with asthma and excessive mucus production. Genetic variation; tobacco smoke and air pollution can upregulate MUC5AC production.
      ORMDL3[29] Regulates endoplasmic reticulum stress and inflammation. It plays a role in maintaining cellular homeostasis and regulating immune response. Variants in ORDLM3 are associated with asthma; particularly, childhood asthma. The gene contributes to airway inflammation and immune response dysregulation by regulating cytokine synthesis and immune cell activation. Genetic variations, incorporating single nucleotide polymorphisms (SNPs); and environmental factors (e.g. allergens) may influence gene expression and immune response.

      Table 1. 

      Genes associated with asthma pathogenesis and their genetic variations.

    • Environmental trigger Percentage of children affected Epigenetic mechanisms involved
      Passive smoking 20%–30% DNA methylation of immune genes (e.g., AHRR, FOXP3), altered miRNA profiles.
      Pollutants from air conditioners ~15% Oxidative stress-driven histone modifications and DNA methylation.
      Pollutants from refrigerators 10%–12% Non-coding RNA dysregulation, DNA methylation of inflammatory pathways.
      Mosquito repellent machines ~10% Disruption of immune gene regulation via non-coding RNAs.
      Vehicle emissions 20%–40% Global hypomethylation, site-specific methylation (e.g., IL-4, IFN-γ genes).

      Table 2. 

      Implications of environmental variables on childhood asthma and pertinent epigenetic initiatives[7].

    • Technique name Corresponding description
      Single-cell RNA sequencing
      (scRNA-seq)      		 Efficient to measure the transcriptome of individual cells further cells are isolated, and RNA is reverse transcribed, and sequenced.
      Single-cell DNA sequencing First in hand to analyze individual cell genomes for mutations, copy number variations, and rearrangements.
      Single-cell epigenomics Studies gene regulation through chromatin accessibility (ATAC-seq), protein-DNA interactions (ChIP-seq), and DNA methylation profiling.
      Spatial transcriptomics Within the tissue architecture, this technique maps gene expression with spatial information.
      Single-cell proteomics Applying advanced mass spectrometry, protein expression, and modifications are measured, as methods like CyTOF.

      Table 3. 

      Techniques favoring the study of cellular diversity, enabling the analysis of heterogeneity in tissues, uncovering rare cell populations.