Genetic and Epigenetic Aspects of Atopic Dermatitis

Abstract

Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.

Keywords: DNA methylation; FLG; SPINK genes; atopic dermatitis; epigenome; genetics; histone modifications; micro-RNA; skin barrier dysfunction.

Figure 1

Etiology of atopic dermatitis.

Figure 2

Epigenetic change in chromatin (promoter methylation, histone methylation, and acetylation) observed in the differentiation process of T helper cells subpopulations (from Potaczek et al. 2017 modified [50].

Figure 3

Factors acting on the body of a pregnant woman and affecting the epigenome of a child. All factors could have a modifying effect.