Genetic Variant in lncZPBP2-3 Associated with Asthma Risk
A LARGE genome-wide association study (GWAS) of individuals of Han Chinese descent has identified a novel long noncoding RNA (lncRNA) variant that may increase susceptibility to asthma, particularly in areas with high air pollution. The study, drawing on genetic and environmental data from more than 100,000 participants in the Taiwan Biobank, provides new insights into how air pollutants interact with the genome to influence asthma development.
Researchers pinpointed a risk region on chromosome 17q12–21 encompassing lncZPBP2-3 and neighbouring genes, already implicated in immune regulation. Elevated expression of lncZPBP2-3 was observed in the blood of individuals with asthma compared to healthy controls. Laboratory analyses demonstrated that the risk variant disrupts normal gene regulation by interfering with the transcription insulator CCCTC-binding factor (CTCF), leading to higher activity of nearby genes linked to inflammatory pathways.
Air Pollution Intensifies Asthma Gene–Environment Interaction
The research team examined 10–15 years of cumulative exposure to fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) to assess environmental interactions. They found that individuals carrying the lncZPBP2-3 risk variant who were exposed to higher levels of PM2.5 and PAHs had a significantly increased risk of developing asthma. In functional experiments, exposure to these pollutants induced the expression of the lncZPBP2-3 risk variant, suggesting that air pollution can amplify the genetic predisposition to asthma.
These findings highlight a novel molecular mechanism by which long-term exposure to air pollutants may trigger or worsen asthma in genetically susceptible individuals. The identification of lncZPBP2-3 as a pollution-responsive lncRNA not only advances understanding of asthma pathogenesis but also underscores the importance of environmental regulation and air quality improvement as public health measures.
The study provides a foundation for exploring lncZPBP2-3 as both a biomarker and potential therapeutic target, bridging the gap between genetics, environmental exposure, and respiratory disease outcomes.
Reference
Liu KY et al. Functional sequence variants of intergenic long noncoding RNA on chromosome 17q21 are associated with asthma. Eur Respir J. 2025;66(4):2500847.