Abnormal DNA methylation in peripheral blood mononuclear cells from patients with vitiligo

P>Background Vitiligo is a skin disorder characterized by the destruction of melanocytes by autoreactive lymphocytes. The genetic and environmental factors that trigger the autoimmune response are poorly understood. However, alterations to epigenetic DNA methylation patterns contribute to many other autoimmune diseases. Objectives To investigate genomic and gene-specific DNA methylation levels in peripheral blood mononuclear cells (PBMCs) of patients with vitiligo and to relate any changes to the expression of genes that regulate methylation, as well as the autoimmune-related gene IL10. Methods We quantified global methylcytosine levels in PBMCs from 20 patients with vitiligo and 20 healthy controls. mRNA levels of DNA methyltransferases (DNMTs), methyl-DNA binding domain proteins (MBDs) and interleukin (IL)-10 were measured by real-time reverse transcriptase-polymerase chain reaction. Methylation of an IL10 regulatory element domain was determined by bisulphite genomic sequencing. Results Genomic DNA methylation in PBMCs of patients with vitiligo was increased relative to healthy controls (P = 0 center dot 012). DNMT1, MBD1, MBD3, MBD4 and MeCP2 expression was significantly higher than in control PBMCs (P = 0 center dot 013, 0 center dot 001, 0 center dot 005, 0 center dot 001 and 0 center dot 001, respectively). MBD1 and MBD3 expression correlated positively with global DNA methylation in vitiligo PBMCs (MBD1: r = 0 center dot 519, P = 0 center dot 019; MBD3: r = 0 center dot 529, P = 0 center dot 016). IL10 expression was significantly decreased (P = 0 center dot 030), and an IL-10 enhancer region was hypermethylated in vitiligo PBMCs compared with controls (P = 0 center dot 014). Conclusions These data show that levels of DNA methylation are altered in PBMCs of patients with vitiligo, and this may contribute to disease activity by affecting the expression of autoimmunity-related genes.