Genetic and Epigenetic Interconnections Between Atopic Dermatitis, Allergic Rhinitis, and Rhinitis with Nasal Polyps

Background: Atopic dermatitis (AD), allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP) represent interconnected conditions within the spectrum of type 2 inflammatory diseases. While these conditions share common genetic and epigenetic pathways, the precise molecular mechanisms remain underexplored. Methods: This review integrates the latest insights on the genetic and epigenetic factors linking AD, AR, and CRSwNP, focusing on genome-wide association studies, DNA methylation patterns, histone modifications, and microRNA regulation. Results: In all three conditions, epigenetic modifications, including DNA methylation (Me) and histone acetylation (Ac) and methylation, regulate inflammatory and barrier-related genes, influencing disease severity. Notably, miRNAs such as miR-146a and miR-155 play pivotal roles in modulating inflammation across all three diseases, while disease-specific miRNAs contribute to airway remodeling (miR-125b and miR-21 in AR and CRSwNP). Emerging evidence underscores the role of microbiome-driven inflammasome activation and matrix metalloproteinases (MMP-2, MMP-9, and MMP-12) in perpetuating chronic inflammation and remodeling. Conclusions: The interplay between genetic predispositions, epigenetic modifications, and exposomal factors underscores the systemic nature of type 2 inflammation. A deeper understanding of these interconnected mechanisms could lead to transformative, personalized diagnostic and therapeutic advancements.