Abstract
Monozygotic (MZ) twins do not show complete concordance for many complex diseases; for example, discordance rates for autoimmune diseases are 20%–80%. MZ discordance indicates a role for epigenetic or environmental factors in disease. We used MZ twins discordant for psoriasis to search for genome-wide differences in DNA methylation and gene expression in CD4+ and CD8+ cells using Illumina's HumanMethylation27 and HT-12 expression assays, respectively. Analysis of these data revealed no differentially methylated or expressed genes between co-twins when analyzed separately, although we observed a substantial amount of small differences. However, combined analysis of DNA methylation and gene expression identified genes where differences in DNA methylation between unaffected and affected twins were correlated with differences in gene expression. Several of the top-ranked genes according to significance of the correlation in CD4+ cells are known to be associated with psoriasis. Further, gene ontology (GO) analysis revealed enrichment of biological processes associated with the immune response and clustering of genes in a biological pathway comprising cytokines and chemokines. These data suggest that DNA methylation is involved in an epigenetic dysregulation of biological pathways involved in the pathogenesis of psoriasis. This is the first study based on data from MZ twins discordant for psoriasis to detect epigenetic alterations that potentially contribute to development of the disease.
Highlights
Psoriasis is a common chronic inflammatory disease, which affects mainly the skin, and the joints
Autoimmune diseases are in general due to a dysregulation of the immune system, and identification of genes involved in alterations of lymphocyte function is essential
We identified many genes involved in the immune response where changes in DNA methylation between unaffected and affected twins correlated with changes in gene expression
Summary
Psoriasis is a common chronic inflammatory disease, which affects mainly the skin, and the joints. Linkage peaks [3], copy number variations (CNVs) [4,5,6] and genes identified by GWAS [7,8,9,10,11,12,13] are associated with psoriasis. The combined effect of these loci does not account for the genetic variation underlying the observed susceptibility to psoriasis, and indicates the involvement of additional genetic, epigenetic or environmental factors [7,14,15]. Further evidence for the role of epigenetic or environmental factors comes from the fact that the concordance rate among MZ twins is only 35–72% [2,14,16]
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