Abstract
Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood. As technology in genome sequencing progressed, scientific efforts were made to explain and predict asthma’s complexity and heterogeneity, and genome-wide association studies (GWAS) quickly became the preferred study method. Several gene markers and loci associated with asthma susceptibility, atopic and childhood-onset asthma were identified during the last few decades. Markers near the ORMDL3/GSDMB genes were associated with childhood-onset asthma, interleukin (IL)33 and IL1RL1 SNPs were associated with atopic asthma, and the Thymic Stromal Lymphopoietin (TSLP) gene was identified as protective against the risk to TH2-asthma. The latest efforts and advances in identifying and decoding asthma susceptibility are focused on epigenetics, heritable characteristics that affect gene expression without altering DNA sequence, with DNA methylation being the most described mechanism. Other less studied epigenetic mechanisms include histone modifications and alterations of miR expression. Recent findings suggest that the DNA methylation pattern is tissue and cell-specific. Several studies attempt to describe DNA methylation of different types of cells and tissues of asthmatic patients that regulate airway remodeling, phagocytosis, and other lung functions in asthma. In this review, we attempt to briefly present the latest advancements in the field of genetics and mainly epigenetics concerning asthma susceptibility.
Highlights
Asthma is a complex, heterogenous but one of the most common respiratory diseases that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood [1]
The EVE Consortium replicated the association between asthma susceptibility and single nucleotide polymorphism (SNP) near IL33 and IL1RL1 [20], later studies showed a strong association with atopic asthma but not with non-atopic asthma [24], while identifying a susceptibility locus near the Thymic Stromal Lymphopoietin (TSLP) gene, where a single SNP showed to be protective against the risk for TH2-asthma
The most optimal way to resolve this issue is by using whole-genome sequencing (WGS), which seems to be superior in accurately determining genotypes of copy number variants (CNVs) and low-frequency variants missed by genome-wide association studies
Summary
Heterogenous but one of the most common respiratory diseases that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood [1]. Several genome-wide association studies (GWAS) have identified numerous genetic variants responsible for asthma susceptibility [2]. These mainly non-coding variants play a regulatory role in gene expression and asthma heritability [3]. The novel field of epigenetics has recently attracted the attention of researchers. Epigenetic changes such as DNA methylation, histone modifications, and microRNA expression have already been studied in several research projects, which could lead to a better understanding of the disease’s mechanisms [4]. We present current knowledge on DNA methylation of different types of immune cells in peripheral blood as well as the alterations in gene methylation in nasal and bronchial epithelium of asthmatic patients
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have