Tuberc Respir Dis.  2020 Jan;83(1):1-13. 10.4046/trd.2018.0088.

Epigenetic Changes in Asthma: Role of DNA CpG Methylation

• Bae DJ
• Jun JA
• Chang HS
• Park JS
• Park CS

• KMID: 2466615
• DOI: http://doi.org/10.4046/trd.2018.0088

Abstract

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the "˜missing' heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

Keyword

Asthma; Gene; Environment; Aspirin; Epigenesis

MeSH Terms

Air Pollutants
Allergens
Aspirin
Asthma*
Base Sequence
DNA Methylation
DNA*
Epigenomics*
Genome
Histone Code
Hypersensitivity
Methylation*
MicroRNAs
Phenotype
Polymorphism, Single Nucleotide
Smoke
Tobacco Products
Air Pollutants
Allergens
Aspirin
DNA
MicroRNAs
Smoke

Figure

• 

  Figure 1 The DNA methylation is the covalent addition of a methyl group to a cytosine residue in a CpG dinucleotide. DNMT: DNA methyltransferase; SAM: S adenosyl methionine.

• 

  Figure 2 The DNA methyltransferase family of enzymes catalyze the transfer of a methyl group to DNA. De novo methyltransferases (DNMT3A and DNMT3B) newly methylate cytosines and express mainly in early embryo development. Maintenance methyltransferases (DNMT1) add methylation to DNA when one strand of DNA is already methylated.

• 

  Figure 3 Differential methylation of CpG sites in bronchial mucosa between Dermatophilosis's species-specific IgE positive atopic and nonatopic asthmatics (A), a network analysis of 54 differentially methylated genes (B). BA: bronchial asthma; NC: normal control.

• 

  Figure 4 Summary of DNA methylation data. (A, B) Volcano plot of differential methylation level between aspirin-induced asthma (AIA) and aspirin-tolerant asthma (ATA) in nasal polyp tissues (A) and buffy coat samples (B). Red dots: delta-beta≥0.5 and p≤0.01, blue dots: delta beta≤−0.5 and p≤0.01, grey dots: −0.5≤Deltabeta≤0.5 and p>0.01. Delta-Beta: difference of DNA methylation level (subtracting the DNA methylation level of ATA from AIA). −log(p): log-transformed t-test p-values. (C) Distribution of the DNA methylation level of AIA and ATA in buffy coat and nasal polyp. Average beta: DNA methylation level (0 to 1). (D) Heatmap of 490 differentially methylated CpGs between AIA and ATA in buffy coat and nasal polyp.

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