Tao Jie, Yang Ming, Chen Zhong, Huang Ying, Zhao Qinjun, Xu Jianhui, Ren He, Zhao Hui, Chen Zhenping, Ren Qian, Yang Renchi
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, People's Republic of China.
J Clin Immunol. 2008 Sep;28(5):432-9. doi: 10.1007/s10875-008-9223-2. Epub 2008 Aug 6.
DNA methylation is known to play an important role in gene transcription and alterations of methylation contribute to the development of certain disorders such as cancer and immunodeficiency. Recent years have found an increasing interest in the role of epigenetic modifications in the etiology of human autoimmune diseases, such as systemic lupus erythromatosus (SLE) and rheumatoid arthritis (RA). DNA methyltransferases (DNMTs) are involved in the epigenetic control of DNA methylation processes. S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, have important indicator action of cellular methylation status. The aim of this study is to explore if DNA methylation plays a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP).
DNMT1, DNMT3A, and DNMT3B mRNA expression in peripheral blood mononuclear cells (PBMCs) of adult ITP patients were analyzed by real-time quantitative polymerase chain reaction. Plasma SAM and SAH levels were assayed with reversed-phase high performance liquid chromatography (HPLC).
DNMT3A and DNMT3B mRNA expressions were significantly lower in ITP patients than in healthy controls (p < 0.001), while DNMT1 mRNA expression was not significantly different between the two groups (p = 0.774). Plasma SAH concentration was significantly elevated in ITP patients than in healthy controls (p < 0.05), while the plasma SAM and SAM/SAH were not significantly different between the two groups (p = 0.133, p = 0.624 respectively).
Our observations suggest that aberrant DNA methylation status reflected by increased plasma SAH concentration and decreased mRNA expression levels of DNMT3A and 3B are possibly involved in the pathogenesis of ITP although the precise mechanisms need further study.
已知DNA甲基化在基因转录中起重要作用，甲基化改变会导致某些疾病如癌症和免疫缺陷的发生。近年来，人们越来越关注表观遗传修饰在人类自身免疫性疾病病因中的作用，如系统性红斑狼疮（SLE）和类风湿关节炎（RA）。DNA甲基转移酶（DNMTs）参与DNA甲基化过程的表观遗传调控。作为细胞必需甲基转移酶反应的底物和产物，S-腺苷甲硫氨酸（SAM）和S-腺苷同型半胱氨酸（SAH）对细胞甲基化状态具有重要的指示作用。本研究旨在探讨DNA甲基化是否在特发性血小板减少性紫癜（ITP）的发病机制中起作用。
采用实时定量聚合酶链反应分析成年ITP患者外周血单个核细胞（PBMCs）中DNMT1、DNMT3A和DNMT3B mRNA的表达。用反相高效液相色谱法（HPLC）检测血浆SAM和SAH水平。
ITP患者的DNMT3A和DNMT3B mRNA表达明显低于健康对照组（p < 0.001），而两组间DNMT1 mRNA表达无明显差异（p = 0.774）。ITP患者血浆SAH浓度明显高于健康对照组（p < 0.05），而两组间血浆SAM及SAM/SAH无明显差异（分别为p = 0.133，p = 0.624）。
我们的观察结果表明，血浆SAH浓度升高以及DNMT3A和3B mRNA表达水平降低所反映的异常DNA甲基化状态可能参与了ITP的发病机制，尽管确切机制有待进一步研究。
