DNA methylation profile and expression of the phyllagrin gene in patients with atopic dermatitis: case-control study

Abstract

Background: Atopic dermatitis (AtD) is one of the most common inflammatory skin diseases, affecting up to 20,0% of children and 2,0–8,0% of adults worldwide. Patients with atopic dermatitis usually have dry skin and itching, they are at higher risk of developing asthma, as well as allergic rhinitis. Features of the clinical course of AtD are associated with both interaction of genes and influence of environmental factors. Studying epigenetic mechanisms could provide understanding of the most likely mechanisms by which environmental factors influence gene expression and contribute to the development of AtD. The aim of the study is to conduct a comprehensive molecular genetic analysis (assessment of the level of global DNA methylation and expression of the filaggrin gene (FLG)) in patients with moderate to severe AtD. Material and methods: The case-control study was conducted from January, 2022, through June 2022. A total of 32 patients with AtD and 6 healthy volunteers were recruited. The level of global DNA methylation in blood samples of patients with AtD and healthy individuals was assessed. The filaggrin gene (FLG) expression was measured by polymerase chain reaction in blood samples. Results: A hypermethylation of the genome in patients with AtD is 2.3 times higher than the methylation of genome in controls (p=0,003). FLG gene (exon 3 position 7-8 and exon 1) expression in patients with AtD is decreased compared to control group. Conclusion: Interaction between genomic changes which are associated with mutations in key barrier and immune genes and environmental factors plays a fundamental role in the AtD pathogenesis. The current study found that the epigenome of AtD patients differs from healthy individuals. The study of pathogenetic mechanisms is the basis for the development of new methods of targeted therapy for this socially significant dermatosis.