Department of Biology, University of Rome "Tor Vergata," Rome.
Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome.
J Gerontol A Biol Sci Med Sci. 2018 May 9;73(6):737-744. doi: 10.1093/gerona/glx198.
Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the aging process including dysregulation of immune system. Beyond the causative genetic defect, DS persons display epigenetic alterations, particularly aberrant DNA methylation patterns that can contribute to the heterogeneity of the disease. In the present work, we investigated the levels of 5-hydroxymethylcytosine and of the Ten-eleven translocation dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in aging. Analyses were carried out on peripheral blood mononuclear cells of DS volunteers enrolled in the context of the MARK-AGE study, a large-scale cross-sectional population study with subjects representing the general population in eight European countries. We observed a decrease in 5-hydroxymethylcytosine, TET1, and other components of the DNA methylation/demethylation machinery in DS subjects, indicating that aberrant DNA methylation patterns in DS, which may have consequences on the transcriptional status of immune cells, may be due to a global disturbance of methylation control in DS.
唐氏综合征（DS）是由 21 号染色体部分或全部额外拷贝引起的，这种现象可能导致疾病的广泛临床表型。DS 的大多数临床特征都是衰老过程的典型特征，包括免疫系统失调。除了致病的遗传缺陷外，DS 患者还表现出表观遗传改变，特别是异常的 DNA 甲基化模式，这可能导致疾病的异质性。在本工作中，我们研究了 5-羟甲基胞嘧啶和 Ten-eleven 易位双加氧酶的水平，这些酶参与 DNA 去甲基化过程，在病理条件和衰老过程中经常失调。对参与 MARK-AGE 研究的 DS 志愿者的外周血单个核细胞进行了分析，该研究是一项具有代表性的 8 个欧洲国家普通人群的大型横断面人群研究。我们观察到 DS 患者的 5-羟甲基胞嘧啶、TET1 和其他 DNA 甲基化/去甲基化机制的成分减少，表明 DS 中异常的 DNA 甲基化模式可能对免疫细胞的转录状态产生影响，这可能是由于 DS 中甲基化控制的整体紊乱所致。
