Hidradenitis suppurativa presents a methylome dysregulation capable to explain the pro-inflammatory microenvironment: Are these DNA methylations potential therapeutic targets?

Autor: Radhakrishna U; Department of Obstetrics and Gynaecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA., Ratnamala U; Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, India., Jhala DD; Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, India.; Department of Zoology, School of Sciences, Gujarat University, Ahmedabad, India., Uppala LV; College of Information Science & Technology, The University of Nebraska at Omaha, Peter Kiewit Institute, Omaha, Nebraska, USA., Vedangi A; Department of Clinical Research, KIMS ICON Hospital, A Unit of ICON Krishi Institute Medical Sciences, Visakhapatnam, India., Patel M; Bioinformatics, Gujarat University, Ahmedabad, India., Vadsaria N; Bioinformatics, Gujarat University, Ahmedabad, India., Shah S; Department of Obstetrics and Gynaecology, B.J. Medical College, Ahmedabad, India., Saiyed N; Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, India., Rawal RM; College of Information Science & Technology, The University of Nebraska at Omaha, Peter Kiewit Institute, Omaha, Nebraska, USA., Mercuri SR; Unit of Clinical Dermatology, Università Vita-Salute San Raffaele, Milan, Italy.; Italian Center of Precisione Medicine and Chronic Inflammation, Milan, Italy., Jemec GBE; Department of Dermatology, Zealand University Hospital, Roskilde, Denmark., Damiani G; Unit of Clinical Dermatology, Università Vita-Salute San Raffaele, Milan, Italy.; Italian Center of Precisione Medicine and Chronic Inflammation, Milan, Italy.; Clinical Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.; Young Dermatologists Italian Network, Milan, Italy.
Jazyk: angličtina
Zdroj: Journal of the European Academy of Dermatology and Venereology : JEADV [J Eur Acad Dermatol Venereol] 2023 Oct; Vol. 37 (10), pp. 2109-2123. Date of Electronic Publication: 2023 Jul 14.
DOI: 10.1111/jdv.19286
Abstrakt: Background: Hidradenitis suppurativa (HS) is a chronic, systemic, inflammatory skin condition with elusive pathogenesis that affects therapeutic intervention directly.
Objective: To characterize epigenetic variations in cytokines genes contributing to HS.
Methods: Epigenome-wide DNA methylation profiling with the Illumina Epic array was performed on blood DNA samples from 24 HS patients and 24 age- and sex-matched controls to explore DNA methylation changes in cytokine genes.
Results: We identified 170 cytokine genes including 27 hypermethylated CpG sites and 143 genes with hypomethylated sites respectively. Hypermethylated genes, including LIF, HLA-DRB1, HLA-G, MTOR, FADD, TGFB3, MALAT1 and CCL28; hypomethylated genes, including NCSTN, SMAD3, IGF1R, IL1F9, NOD2, NOD1, YY1, DLL1 and BCL2 may contribute to the pathogenesis of HS. These genes were enriched in the 117 different pathways (FDR p-values ≤ 0.05), including IL-4/IL-13 pathways and Wnt/β-catenin signalling.
Conclusions: The lack of wound healing, microbiome dysbiosis and increased tumour susceptibility are all sustained by these dysfunctional methylomes, hopefully, capable to be targeted in the next future. Since methylome describes and summarizes genetic and environmental contributions, these data may represent a further step towards a feasible precision medicine also for HS patients.
(© 2023 European Academy of Dermatology and Venereology.)
Databáze: MEDLINE
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