DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

Abstract

The study of epigenetics has improved our understanding of mechanisms underpinning gene‐environment interactions and is providing new insights in the pathophysiology of respiratory allergic diseases. We reviewed the literature on DNA methylation patterns across different tissues in asthma and/or rhinitis and attempted to elucidate differentially methylated loci that could be used to characterize asthma or rhinitis. Although nasal and bronchial epithelia are similar in their histological structure and cellular composition, genetic and epigenetic regulation may differ across tissues. Advanced methods have enabled comprehensive, high‐throughput methylation profiling of different tissues (bronchial or nasal epithelial cells, whole blood or isolated mononuclear cells), in subjects with respiratory conditions, aiming to elucidate gene regulation mechanisms and identify new biomarkers. Several genes and CpGs have been suggested as asthma biomarkers, though research on allergic rhinitis is still lacking. The most common differentially methylated loci presented in both blood and nasal samples are ACOT7, EPX, KCNH2, SIGLEC8, TNIK, FOXP1, ATPAF2, ZNF862, ADORA3, ARID3A, IL5RA, METRNL and ZFPM1. Overall, there is substantial variation among studies, (i.e. sample sizes, age groups and disease phenotype). Greater variability of analysis method detailed phenotypic characterization and age stratification should be taken into account in future studies.

The complexity in DNA methylation analysis of allergic diseases

“…Big data with similar cohorts are existing, and maybe it is the time to organize and reanalyze all of them in multiparametric models, taking into account all the factors known to be implicated. In our recent review, reporting DNAm results according to tissue specificity, we had identified a small number of differentially methylated loci common in blood and nasal samples that are annotated to specific genes ( ACOT7 , EPX , KCNH2 , SIGLEC8 , TNIK , FOXP1 , ATPAF2 , ZNF8s62 , ADORA3 , ARID3A , IL5RA , METRNL , ZFPM1 ), making them possible candidates for allergic respiratory disease biomarkers [47]. In the present review, combining the information of different tissues and different associated functions that appear to play decisive roles in development/distinguishing of allergic diseases, we can highlight specific genes.…”

Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma

“…Finally, it is also worth highlighting that methylation patterns could be continually changing with ageing, Tanner stage, asthma severity, and the evolution time of asthma [ 36 , 37 ]. For example, ageing is characterised by global hypomethylation and regions of CpG island hypermethylation [ 36 , 37 ]. These modifications in epigenetics might generate lower gene promoter methylation status in older adolescents.…”

Epigenetic modifications in chronic rhinosinusitis with and without nasal polyps

“…Epigenetic changes may pass down over two generations, as shown by a murine transgenerational asthma model ( Jahreis et al, 2018 ). Scholars have highlighted the significance of epigenetics in the pathogenesis of asthma and other allergic disorders, suggesting a probability of using epidrugs for prevention ( Legaki et al, 2022 ; Potaczek et al, 2022 ). Epigenetic mechanisms may be initiated to dysregulate transcription factors involved in the activities of T lymphocytes and other immune cells, ultimately resulting in asthma and allergic disease ( Liu et al, 2020b ).…”