Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, United States.
Schizophr Res. 2013 Oct;150(1):312-8. doi: 10.1016/j.schres.2013.07.030. Epub 2013 Aug 12.
The epigenetic dysregulation of the brain genome associated with the clinical manifestations of schizophrenia (SZ) includes altered DNA promoter methylation of several candidate genes. We and others have reported that two enzymes that belong to the DNA-methylation/demethylation network pathways-DNMT1 (DNA-methyltransferase) and ten-eleven translocator-1(TET1) methylcytosine deoxygenase are abnormally increased in corticolimbic structures of SZ postmortem brain. The objective of this study was to investigate whether the expression of these components of the DNA-methylation-demethylation pathways known to be altered in the brain of SZ patients are also altered in peripheral blood lymphocytes (PBL). The data show that increases in DNMT1 and TET1 and in glucocorticoid receptor (GCortR) and brain derived neurotrophic factor (BDNF) mRNAs in PBL of SZ patients are comparable to those reported in the brain of SZ patients. The finding that the expressions of DNMT1 and TET1 are increased and SZ candidate genes such as BDNF and GCortR are altered in the same direction in both the brain and PBL together with recent studies showing highly correlated patterns of DNA methylation across the brain and blood, support the hypothesis that a common epigenetic dysregulation may be operative in the brain and peripheral tissues of SZ patients.
与精神分裂症（SZ）临床表现相关的大脑基因组的表观遗传失调包括几个候选基因的 DNA 启动子甲基化改变。我们和其他人已经报道，属于 DNA 甲基化/去甲基化网络途径的两种酶-DNMT1（DNA-甲基转移酶）和 TET1（十一转移酶-1）甲基胞嘧啶去氧核糖核酸酶，在 SZ 死后大脑的皮质边缘结构中异常增加。本研究的目的是研究已知在 SZ 患者大脑中改变的这些 DNA 甲基化-去甲基化途径的组成部分是否也在外周血淋巴细胞（PBL）中改变。数据显示，SZ 患者 PBL 中的 DNMT1 和 TET1 以及糖皮质激素受体（GCortR）和脑源性神经营养因子（BDNF）mRNA 的增加与在 SZ 患者大脑中报道的增加相当。DNMT1 和 TET1 的表达增加，以及 SZ 候选基因如 BDNF 和 GCortR 的改变在大脑和 PBL 中方向相同，再加上最近的研究表明大脑和血液中的 DNA 甲基化模式高度相关，支持这样一种假说，即共同的表观遗传失调可能在 SZ 患者的大脑和外周组织中起作用。
