Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus
Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus
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DOI：
10.1101/gr.100289.109
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发表时间：
2010-02-01
期刊：
影响因子：
7
通讯作者：
Ballestar, Esteban
中科院分区：
文献类型：
--
作者：
Javierre, Biola M.;Fernandez, Agustin F.;Ballestar, Esteban
同卵双胞胎（MZ）在大多数复杂疾病（包括自身免疫性疾病）中是部分一致的。虽然表型一致性可以用来研究遗传力，不一致性表明非遗传因素的作用。在自身免疫性疾病中，环境驱动的表观遗传变化被认为是其病因的原因。在这里，我们报告了第一个高通量和候选序列分析的DNA甲基化，以调查不一致的自身免疫性疾病的双胞胎。我们使用了一组临床症状经常重叠的三种疾病不一致的同卵双胞胎：系统性红斑狼疮（SLE）、类风湿性关节炎和皮肌炎。只有与SLE不一致的同卵双胞胎的特征是大量基因的DNA甲基化状态发生广泛变化。基因本体分析显示与免疫功能相关的类别丰富。个体分析证实SLE发病相关基因存在DNA甲基化和表达改变。这些变化与5-甲基胞嘧啶含量的总体降低平行发生，5-甲基胞嘧啶含量的总体降低伴随着DNA甲基化和核糖体RNA基因表达水平的变化，我们的研究结果不仅确定了SLE患者临床特征的潜在相关DNA甲基化标志物，而且支持了表观遗传学变化可能在SLE患者中起关键作用的观点。自身免疫性疾病的临床表现。
Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.