Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
J Invest Dermatol. 2012 Mar;132(3 Pt 1):583-92. doi: 10.1038/jid.2011.348. Epub 2011 Nov 10.
Psoriasis is a chronic inflammatory immune-mediated disorder affecting the skin and other organs including joints. Over 1,300 transcripts are altered in psoriatic involved skin compared with normal skin. However, to our knowledge, global epigenetic profiling of psoriatic skin is previously unreported. Here, we describe a genome-wide study of altered CpG methylation in psoriatic skin. We determined the methylation levels at 27,578 CpG sites in skin samples from individuals with psoriasis (12 involved, 8 uninvolved) and 10 unaffected individuals. CpG methylation of involved skin differed from normal skin at 1,108 sites. Twelve mapped to the epidermal differentiation complex, upstream or within genes that are highly upregulated in psoriasis. Hierarchical clustering of 50 of the top differentially methylated (DM) sites separated psoriatic from normal skin samples with uninvolved skin exhibiting intermediate methylation. CpG sites where methylation was correlated with gene expression are reported. Sites with inverse correlations between methylation and nearby gene expression include those of KYNU, OAS2, S100A12, and SERPINB3, whose strong transcriptional upregulation is an important discriminator of psoriasis. Pyrosequencing of bisulfite-treated DNA from skin biopsies at three DM loci confirmed earlier findings and revealed reversion of methylation levels toward the non-psoriatic state after 1 month of anti-TNF-α therapy.
银屑病是一种慢性炎症性免疫介导性疾病，影响皮肤和其他器官，包括关节。与正常皮肤相比，银屑病患者的皮肤中有超过 1300 个转录本发生改变。然而，据我们所知，以前尚未报道过银屑病皮肤的全基因组表观遗传谱分析。在这里，我们描述了一项针对银屑病皮肤中 CpG 甲基化改变的全基因组研究。我们测定了来自银屑病患者（12 例受累，8 例未受累）和 10 例未受影响个体的皮肤样本中 27578 个 CpG 位点的甲基化水平。受累皮肤的 CpG 甲基化在 1108 个位点与正常皮肤不同。其中 12 个位于表皮分化复合物内或附近，这些基因在银屑病中高度上调。50 个差异甲基化（DM）位点的层次聚类将银屑病与正常皮肤样本分开，未受累皮肤表现出中间甲基化。报告了与基因表达相关的 CpG 位点。与附近基因表达呈负相关的位点包括 KYNU、OAS2、S100A12 和 SERPINB3 的位点，它们的强转录上调是银屑病的一个重要鉴别特征。对三个 DM 位点皮肤活检的亚硫酸氢盐处理 DNA 的焦磷酸测序证实了早期的发现，并显示在接受抗 TNF-α 治疗 1 个月后，甲基化水平向非银屑病状态逆转。
