Epigenetics in asthma: implications for treatable traits.

Abstract

Epigenetic mechanisms refer to heritable and potentially reversible modifications that regulate chromatin architecture and gene expression without altering the underlying DNA sequence. In asthma, these mechanisms provide a molecular interface between genetic susceptibility, environmental exposures, and immune dysregulation, contributing to disease heterogeneity and treatment response. The treatable traits paradigm, which focuses on the identification of specific modifiable biological and clinical characteristics, offers a clinically relevant framework for linking epigenetic changes to distinct molecular endotypes, enhancing mechanistic stratification beyond traditional phenotyping, thereby supporting precision medicine approaches. Emerging evidence suggests that epigenetic signatures have considerable potential as biomarkers for inflammatory endotyping and therapeutic stratification, although further validation is required before routine clinical implementation. In this mini review we will discuss epigenetic mechanisms involved in the development and maintenance of asthma processes, such as DNA methylation, histone modifications, and noncoding RNAs, focusing on their relevance to key treatable traits, including type 2 inflammation, corticosteroid responsiveness, airway remodeling, and exposure-driven disease.