DNA Methylation Analysis of Lesional and Non-lesional Skin in Adult Patients with Atopic Dermatitis

DOI: https://doi.org/10.29296/24999490-2021-01-08

O.Yu. Smolkina(1), E.P. Bystritskaia(2), O.А. Svitich(2), A.L. Piruzyan(1), E.V. Denisova(1, 3), I.M. Korsunskaya(1), V.V. Sobolev(1, 2) 1-Center for Theoretical Problems of Physico-chemical Pharmacology of the Russian Academy of Sciences, Srednyaya Kalitnikovskaya str., 30, Moscow, 109029, Russian Federation; 2-I.I. Mechnikov Research Institute for Vaccines and Sera, Malуy Kazenny bystr., 5, Moscow, 105064, Russian Federation; 3-Moscow Scientific – and – Practical Center for Dermatovenereology and Cosmetology, Healthcare Department, Seleznevskaya st. 20, Moscow, 127473, Russian Federation E-mail: [email protected]

Introduction. Atopic dermatitis is a chronic inflammatory disease caused by a complex interaction of genetic, immune, and environmental factors. Recently, the study of epigenetic changes has brought new insights into the etiology of atopic dermatitis. Aim of the study is to investigate the methylation level in affected and unaffected skin biopsies from patients with atopic dermatitis. Methods. DNA isolation was performed using the QIAamp DNA Mini Kit (Qiagen, USA). Bisulfite conversion of the isolated DNA was performed using the EZ DNA Methylation Kit (Zymo Research, USA). DNA methylation levels were studied by hybridization of the converted DNA with BeadChip Infinium Human Methylation450 chips (Illumina, USA). The chips were scanned using the HiScanSQ System (Illumina, USA). The resulting images were analyzed using GenomeStudio® software (version 2011.1; methylation model version 1.9.0, Illumina Inc.). Results. Changes in the methylation levels were revealed in 26 genes, 9 of which were methylated in the promoter region. 11 genes were hypermethylated, 15 genes were hypomethylated. Changes in the level of DNA methylation were observed for genes whose protein products are involved in many biological processes associated with atopic dermatitis: positive regulation of fibroblast migration, proliferation of dendritic cells, and activation of immunity. In the TSS200 region, only ALPK2 gene was hypomethylated in the tissue affected by atopic dermatitis. In contrast; CLNK and ARHGEF4 were hypermethylated. In the TSS1500 region, four genes were hypomethylated: MIR1178, VPS37C, GRIP2, and SLC47A2. The TCF12 and ZBTB20 genes were hypermethylated. Conclusion. The obtained results indicate the involvement of epigenetic regulation in the development of the atopic process. However, the analysis of additional skin samples from new patients is needed to validate and further refine the findings.
Keywords: 
atopic dermatitis, DNA methylation, skin biopsy, genome-wide DNA methylation analysis
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