Genetic susceptibility to respiratory health effects from outdoor air pollution: a structured narrative review.

Outdoor air pollution exposure is a well-established driver of respiratory disease, while growing evidence highlights an important role for genetic susceptibility. Building on this expanding body of work, our review synthesises findings across studies and provides an integrated overview. Here, we present a structured literature review summarising study characteristics and statistically significant single nucleotide polymorphisms (SNPs) reported in gene-environment interaction studies of air pollution related respiratory outcomes. By consolidating this evidence, the review clarifies current findings and supports more rigorous, evidence-based risk stratification in future observational and intervention studies. We included 48 peer-reviewed studies in humans published between 2014 and 2024 that examined gene-environment interactions involving SNPs, outdoor air pollution exposure and respiratory outcomes. Studies primarily evaluating particulate matter with aerodynamic diameter <2.5 µm and <10 μm, and nitrogen dioxide included respiratory end-points, such as asthma, COPD and lung-function measures. The majority of analyses used regression-based methods, supplemented by mixed-effects and generalised estimating equation models. Candidate gene studies (particularly in the glutathione S-transferase (GST) family) along with polygenic risk scores and genome-wide interaction approaches identified 89 SNPs across 53 genes. Replicated variants involved pathways in oxidative stress detoxification (e.g. rs1695 (GSTP1) and rs2266637 (GSTT1)) and inflammatory responses (e.g. rs1800629 (TNF), rs3804099 (TLR2) and rs848 (IL13)), consistently modifying pollution-related lung function decline and airway inflammation. By consolidating key genes, study designs and analytic methods, this review provides a curated SNP list to inform future genetic risk stratification. We highlight the need for studies in ancestrally diverse populations, controlled human exposure designs, and multi-omics approaches to strengthen mechanistic understanding of gene-environment interactions in respiratory health.