Hidradenitis suppurativa presents a methylome dysregulation capable to explain the pro‐inflammatory microenvironment: Are these DNA methylations potential therapeutic targets?
Uppala Radhakrishna, Uppala Ratnamala, Devendrasinh D. Jhala, Lavanya V. Uppala, Aaren Vedangi, Maulikkumar Patel, Nikita Vadsaria, Sushma Shah, Nazia Saiyed, Rakesh M. Rawal, Santo Raffaele Mercuri, Gregor B. E. Jemec, Giovanni Damiani - Infectious Diseases
- Dermatology
Abstract
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.