Genetics and Epigenetics in Asthma

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.

Pyroptosis, metabolism, and tumor immune microenvironment

“…Genome‐wide sequencing and functional genes indicate that single nucleotide polymorphisms of GSDMB are related to the increased susceptibility of ulcerative colitis and Crohn's disease, as well as asthma exacerbations and antiviral pathways. 106 , 112 , 149 Analogous to GSDMA, GSDMB is also linked to childhood‐onset asthma, 154 while GSDMB (rs9303277) in CD4 + T cells is an SSc‐associated susceptibility locus. 115 In addition, GSDMB is included in the Type 1 and 2 diabetes (T1D, T2D) islet expression quantitative trait loci interaction network.…”

Airway Wall Remodeling in Childhood Asthma—A Personalized Perspective from Cell Type-Specific Biology

“…Other studies suggested that the many pathologies that characterized asthma might be explained by epigenetic imprinting of the developing lung during embryogenesis and early childhood [17,18]. The best studied epigenetic mechanisms related to asthma are histone modification, DNA methylation, and altered expression of specific micro RNAs (Figure 2).…”

“…Referring to some studies on the causes of airway wall remodeling during embryogenesis and early childhood [10][11][12], this hypothesis has been challenged [13][14][15][16][17]. The earlier assumption that asthma, atopy, and bronchial hyper-reactivity are caused by genetic modifications of immune regulatory proteins was not confirmed [13,18]. Nearly twenty years ago, the significantly increased thickness of the lamina reticularis due to increased collagen deposition correlated with the expression of the epidermal growth factor receptor, but without eosinophilic infiltration in children with asthma [14].…”

“…The release of neuropeptides may occur through epigenetic events triggered by environmental factors during embryogenesis and early childhood, which may trigger airway wall remodeling [10,12]. Importantly, such events can be inherited and, thus, mimic genetic traits [18]. This review summarizes the current knowledge on airway wall remodeling in asthma with a specific focus on childhood asthma.…”

Viral Infection and Respiratory Exacerbation in Children: Results from a Local German Pediatric Exacerbation Cohort

“…Asthma is still one of the most common respiratory diseases [1,2], with 262 to 340 million cases worldwide, including 800,000 affected children living in Germany and a region-dependent incidence [3][4][5][6][7][8] associated with a high number of undiagnosed cases [9][10][11][12]. Based on the German national guidelines, the NVL Asthma 2020 (=Nationale Versorgungsleitlinie Asthma 2020), severe asthma exacerbation is defined by tachypnea, tachycardia, peak expiratory flow variations, reduced oxygen saturation, or speech dyspnea [13].…”