Geneva University Hospitals, Department of Medical Genetics and Laboratory, 2 ch Petit Bel-Air, 1225 Chêne-Bourg, Switzerland.
J Affect Disord. 2011 Aug;132(3):450-3. doi: 10.1016/j.jad.2011.03.018. Epub 2011 Mar 30.
Epigenetic changes may play a role in the etiology of psychotic diseases. It has been demonstrated that the serotonin receptor, 5HTR1A, is implicated in schizophrenia (SCZ) and bipolar disorder (BPD). The aim of this study was to investigate the methylation status of a promoter region of the 5HTR1A gene in BPD and SCZ patients.
Our study included 58 BPD and 40 SCZ (DSM-IV criteria) as well as 67 control subjects. DNA was extracted from blood leukocytes and high-resolution melt (HRM) method was used for analysis.
Non-parametric analysis of variance (Kruskal-Wallis) within groups was significant: H=67.6; p<0.0001. The Mann-Whitney U-test showed increased methylation level in both BPD (Z=-7.4; p<0.0001) and SCZ (Z=4.2; p<0.0001) compared to controls. No effect either of age or gender by own, was observed. ANCOVA revealed a modest effect of age/gender covariance (F=3.99; p<0.048).
We used a peripheral tissue. The relationship between methylation of blood and brain DNA is not well known. Data need to be replicated in a brain tissue.
We observed increased DNA methylation in the promoter region of the 5HTR1A gene of SCZ and BPD. This could explain the reported decrease of the receptor expression. The current study supports the growing interest of DNA methylation in psychopathology.
表观遗传改变可能在精神疾病的发病机制中起作用。已经证明，5-羟色胺受体 5HTR1A 与精神分裂症（SCZ）和双相情感障碍（BPD）有关。本研究旨在研究 BPD 和 SCZ 患者中 5HTR1A 基因启动子区域的甲基化状态。
我们的研究包括 58 名 BPD 和 40 名 SCZ（DSM-IV 标准）以及 67 名对照。从血液白细胞中提取 DNA，并使用高分辨率熔解（HRM）方法进行分析。
组内非参数方差分析（Kruskal-Wallis）具有统计学意义：H=67.6；p<0.0001。Mann-Whitney U 检验显示，与对照组相比，BPD（Z=-7.4；p<0.0001）和 SCZ（Z=4.2；p<0.0001）的甲基化水平均升高。未观察到年龄或性别本身的影响。协方差分析显示年龄/性别协方差的适度影响（F=3.99；p<0.048）。
我们使用了外周组织。血液和大脑 DNA 甲基化之间的关系尚不清楚。需要在脑组织中复制数据。
我们观察到 SCZ 和 BPD 中 5HTR1A 基因启动子区域的 DNA 甲基化增加。这可以解释报道的受体表达减少。本研究支持 DNA 甲基化在精神病理学中的日益增长的兴趣。
