Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China.
Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China.
J Invest Dermatol. 2016 Apr;136(4):779-787. doi: 10.1016/j.jid.2015.12.029. Epub 2015 Dec 29.
Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni < 0.01; methylation level difference > 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis.
银屑病是一种由遗传和环境因素相互作用引起的慢性过度增生和炎症性皮肤病。DNA 甲基化与银屑病有关，但这一过程如何导致疾病尚不完全清楚。在这项研究中，我们进行了三阶段的表观基因组全关联研究，使用 262 个皮肤和 48 个外周血单核细胞样本的组合，确定与疾病相关的差异甲基化位点。我们不仅揭示了银屑病的全基因组甲基化模式，还发现了九个与疾病相关的差异甲基化位点的皮肤特异性 DNA 甲基化与银屑病之间的强烈关联（Wilcoxon 秩和检验 PBonferroni < 0.01；甲基化水平差异 > 0.10）。进一步的分析表明，这九个与疾病相关的差异甲基化位点不受遗传变异的显著影响，支持它们对疾病状态的显著贡献。CYP2S1、ECE1、EIF2C2、MAN1C1 和 DLGAP4 的表达与 DNA 甲基化呈负相关。这些发现将有助于我们更好地理解银屑病的分子机制。
