Zhang Yuqi, Chang Zaohuo, Chen Jionghua, Ling Yang, Liu Xiaowei, Feng Zhang, Chen Caixia, Xia Minghua, Zhao Xingfu, Ying Wang, Qing Xu, Li Guilin, Zhang Changsong
Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
Department of Brain, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Mol Med Rep. 2015 Aug;12(2):3184-90. doi: 10.3892/mmr.2015.3748. Epub 2015 May 7.
Tryptophan hydroxylase-2 (TPH2) contributes to alterations in the function of neuronal serotonin (5-HT), which are associated with various psychopathologies, including major depressive disorder (MDD) or suicidal behavior. The methylation of a single CpG site in the promoter region of TPH2 affects gene expression. Suicide and MDD are strongly associated and genetic factors are at least partially responsible for the variability in suicide risk. The aim of the present study was to investigate whether variations in TPH2 methylation in peripheral blood samples may predispose patients with MDD to suicide attempts. TPH2 mRNA expression levels differed significantly between 50 patients with MDD who had attempted suicide (MDD + suicide group) and 75 control patients with MDD (MDD group); TPH2 expression levels were significantly decreased (P=0.0005) in the patients who had attempted suicide. Furthermore, the frequency of TPH2 methylation was 36.0% in the MDD + suicide group, while it was 13.0% in the MDD group. The results of the present study demonstrated that methylation in the promoter region of TPH2 significantly affected the mRNA expression levels of TPH2, thus suggesting that methylation of the TPH2 promoter may silence TPH2 mRNA expression in MDD patients with or without suicidal behavior. In addition, there was a significant correlation between the methylation status of the TPH2 promoter and depression, hopelessness and cognitive impairment in the MDD + suicide group. In conclusion, the present study demonstrated that TPH2 expression was regulated by DNA methylation of the TPH2 promoter region in patients with MDD.
色氨酸羟化酶-2（TPH2）会导致神经元5-羟色胺（5-HT）功能改变，这与包括重度抑郁症（MDD）或自杀行为在内的多种精神病理学有关。TPH2启动子区域单个CpG位点的甲基化会影响基因表达。自杀与MDD密切相关，遗传因素至少部分导致了自杀风险的差异。本研究的目的是调查外周血样本中TPH2甲基化的变化是否会使MDD患者易发生自杀未遂。50例有自杀未遂的MDD患者（MDD+自杀组）与７５例MDD对照患者（MDD组）之间TPH2 mRNA表达水平存在显著差异；自杀未遂患者的TPH2表达水平显著降低（P = 0.0005）。此外，MDD+自杀组中TPH2甲基化频率为36.0%，而MDD组为13.0%。本研究结果表明，TPH2启动子区域的甲基化显著影响TPH2的mRNA表达水平，这表明TPH2启动子的甲基化可能会使有或无自杀行为的MDD患者中TPH2 mRNA表达沉默。此外，MDD+自杀组中TPH2启动子的甲基化状态与抑郁、绝望和认知障碍之间存在显著相关性。总之，本研究表明MDD患者中TPH2的表达受TPH2启动子区域DNA甲基化的调控。
