The role of DNA methylation in the pathogenesis of allergic rhinitis

Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E, with its global prevalence exhibiting a persistent upward trend. This review elucidates the pivotal role of DNA methylation, a fundamental epigenetic mechanism, in the pathogenesis of AR. Serving as a crucial interface between environmental exposures and genetic susceptibility, DNA methylation provides a molecular framework for understanding gene-environment interactions in this complex disease.The article systematically examines the multifaceted involvement of DNA methylation in AR. It details how epigenetic modifications contribute to the intergenerational transmission of disease risk, highlighting evidence for both maternal and paternal influences through specific gene methylation patterns. A significant portion is devoted to dissecting how various environmental factors, including airborne pollutants (e.g., PM2.5), microbial exposures, and allergens (e.g., pollen, house dust mites), can dynamically alter the DNA methylome. These alterations subsequently dysregulate the expression of key immune-related genes.The review further delves into the mechanistic consequences of these methylation changes. It summarizes how aberrant methylation of critical genes—such as those within the FOX family (e.g., FOXP3), cytokines (e.g., IL13, IFN-γ), and others (e.g., LPCAT2)—disrupts immune homeostasis. This disruption predominantly manifests as a Th1/Th2 imbalance, characterized by suppressed Th1 responses and amplified Th2 activity, leading to the hallmark inflammation and symptoms of AR. Notably, the reversible nature of DNA methylation presents a promising therapeutic avenue. The potential of DNA methyltransferase inhibitors, widely used in oncology, is discussed for their capacity to reverse pathological methylation patterns, restore immune balance, and potentially treat AR.Despite the promising insights, the review acknowledges current limitations, such as relatively small-scale studies, a focus often broader than AR-specific mechanisms, and an incomplete understanding of the precise pathways linking environmental triggers to specific methylation changes. In conclusion, DNA methylation stands as a central regulator in AR pathogenesis. Profiling DNA methylation patterns holds significant promise for developing novel diagnostic biomarkers, enabling precise disease stratification, and guiding the development of targeted epigenetic therapies, ultimately contributing to improved prevention and management strategies for AR.