Epigenetics and its role in development and regulation of allergy — a systematic review

BACKGROUND: Epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNAs have more recently been highlighted as important regulatory elements of gene expression in allergic diseases. Such mechanisms mediate interactions between predisposing genetic determinants and environmental exposures, with subsequent influences on immune response as well as on susceptibility to conditions such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. MATERIALS AND METHODS: This systematic review integrated evidence from studies exploring the role of epigenetic modifications in allergic diseases. The databases were searched systematically and relevant studies as per predefined PECOS criteria were included. All data regarding epigenetic mechanisms, the target loci involved, environmental influences, and allergic outcomes were extracted and analyzed. The studies were evaluated for risk of bias using the RoB 2.0 and ROBINS-I tools, and the certainty of evidence was appraised using the GRADE framework. RESULTS: It was observed that DNA methylation at such loci, including FOXP3 and IL-4Rα, was invariably associated with immune dysregulation in allergic diseases across the 11 studies included. Exposure to pollutants and microbial exposure has shown associations with alterations in epigenetic profiles that have resulted in significant impacts on immune tolerance and allergic inflammation. Quantitative results: in specific immunotherapy settings, 95 % suppression of effector T-cell proliferation (p 0.0001), and identification of 956 CpG sites associated with the risk of allergic rhinitis Fixed drug reaction (FDR) 5 %. The studies together showed that epigenetic modifications are central to the pathogenesis of allergic diseases and may be used as biomarkers and therapeutic targets. CONCLUSION: This review highlighted how epigenetics played a crucial role in the development and regulation of allergic diseases and underlined the interactions between these entities and environmental exposures. Findings indicated that epigenetic mechanisms promise a wide potential in precision medicine, mainly concerning biomarker discovery and treatment stratification. However, study methodology heterogeneity and variability of results should be pursued further for homogenization of methodologies and thus increasing the applicability in clinics.