title: Epigenetics in the pathogenesis and pathophysiology of psoriasis vulgaris.
abstract: Epigenetic phenomena, including DNA methylation, histone modification, and genetic regulation by miRNAs, are potentially heritable genetic regulatory changes that are not attributed to direct alterations in the DNA sequence of base pairs. They may explain the link between psoriasis risk alleles and disease development, as alleles possess various potentials to undergo epigenetic modification. Multiple genes involved in psoriasis pathogenesis demonstrate abnormal methylation patterns including those involved in epidermal differentiation and proliferation, immunity, the cell cycle, apoptosis, inflammation, and IFN-γ and TNF-α signaling. Hypoacetylation of histone H4 is observed in peripheral blood mononuclear cells of psoriatic patients, and the degree of hypoacetylation of histone H4 is inversely correlated to the PASI score. Investigators have reported both increased and decreased expression of miRNAs in patients with psoriasis, and have described and speculated a number of possible mechanisms for their roles in pathogenesis. Interestingly, the altered methylation patterns observed in psoriasis appear to be normalized by treatment with biologics directed at TNF-α inhibition. However, attempts to directly correlate epigenetic regulatory mechanisms with expression of genes observed in psoriasis have been limited thus far, and correlating miRNA expression levels to disease phenotypes can be challenging and inconsistent. Hopefully, the goal of drawing clinically relevant conclusions about the role of epigenetics in psoriasis will be aided by recent methods that enable fast and sensitive epigenomic profiling. Drugs targeting epigenetic mechanisms are currently being explored, though not for psoriasis, but specificity to pathogenetic mechanisms remains elusive. However, the amenability of cutaneous disease to topical therapies may elevate their usefulness in the treatment of this common skin disorder.
authors: Ryan M
authors: RM
authors: Trowbridge
authors: Mark R
authors: MR
authors: Pittelkow
mesh_terms: D000483:Alleles; D019175:DNA Methylation / Q000235:genetics; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D044127:Epigenesis, Genetic; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D058990:Molecular Targeted Therapy; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D003879:Dermatologic Agents; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha