Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: A potential link between epigenetics and schizophrenia
Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: A potential link between epigenetics and schizophrenia
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DOI：
10.1016/j.jpsychires.2006.08.006
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Okazaki, Yuji
中科院分区：
文献类型：
--
作者：
Shimabukuro, Morihiro;Sasaki, Tsukasa;Okazaki, Yuji
遗传和表观遗传因素可能会改变对精神分裂症等精神疾病的易感性。为了探讨表观遗传学对精神分裂症发病机制的影响，我们检测了 210 名精神分裂症患者（124 名男性和 86 名女性）和 237 名健康受试者（108 名男性和 129 名女性）的白细胞 DNA 总体甲基化水平。采用高效液相色谱法 (HPLC) 测定外周血白细胞 DNA 中甲基化脱氧胞苷 (mC) 的含量。我们在健康受试者中证实了我们之前的发现，除了年龄的影响（β = -0.141，p = 0.022）外，mC 含量还存在性别依赖性差异（男性 > 女性；β = 0.319，p < 0.001）。因此，我们使用多元回归来按性别分析所有受试者的数据，并以年龄作为协变量。在男性中，观察到患者的 mC 含量比对照组低（β = -0.115，p = 0.075），年龄影响显着（β = -0.212，p < 0.001）。这种差异在年轻人中更为明显。在女性中，没有观察到年龄或疾病状况对 mC 含量的影响。这些结果证实，人外周血白细胞DNA的mC含量存在显着的性别依赖性差异，并提出了精神分裂症患者中存在DNA甲基化状态改变的可能性。 (c) 2006 Elsevier Ltd. 保留所有权利。
Genetic and epigenetic factors can potentially alter susceptibility to psychiatric disorders such as schizophrenia. In order to explore the effect of epigenetics on the pathogenesis of schizophrenia, we examined the global methylation level of leukocyte DNA from 210 patients with schizophrenia (124 males and 86 females) and 237 healthy subjects (108 males and 129 females). Methylated deoxycytidine (mC) content in peripheral leukocyte DNA was measured by high performance liquid chromatography (HPLC). We confirmed in the healthy subjects our previous finding that there are sex-dependent differences in mC content (males > females; beta = 0.319, p < 0.001), in addition to the effect of age (beta = -0.141, p = 0.022). We therefore used multiple regression to analyze the data from all subjects by sex, with age as a co-variant. In males, a tendency was observed toward lower mC content in patients than in controls (beta = -0.115, p = 0.075), with a significant effect of age (beta = -0.212, p < 0.001). This difference was more prominent in younger individuals. In females, no effect of age or disease status on mC content was observed. These results established that there is significant sex-dependent difference in the mC content of human peripheral leukocyte DNA, and raise the possibility that alterations in DNA methylation state are present in patients with schizophrenia. (c) 2006 Elsevier Ltd. All rights reserved.