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The pathogenesis of many diseases is influenced by environmental factors which can affect human genome and be inherited from generation to generation. Adverse environmental stimuli are recognized through the epigenetic regulatory complex, leading to gene expression alteration, which in turn culminates in disease outcomes. Three epigenetic regulatory mechanisms modulate the manifestation of a gene, namely DNA methylation, histone changes, and microRNAs. Both epigenetics and genetics have been implicated in the pathogenesis of systemic sclerosis (SSc) disease. Genetic inheritance rate of SSc is low and the concordance rate in both monozygotic (MZ) and dizygotic (DZ) twins is little, implying other possible pathways in SSc pathogenesis scenario. Here, we provide an extensive overview of the studies regarding different epigenetic events which may offer insights into the pathology of SSc …