title: Methylation of the tryptophan hydroxylase‑2 gene is associated with mRNA expression in patients with major depression with suicide attempts.
abstract: 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.
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Zaohuo
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Department of Brain, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
authors.forename: Jionghua
authors.initials: J
authors.lastname: Chen
authors.affiliation: Clinical Oncology Laboratory, Changzhou Cancer Hospital of Soochow University, Changzhou, Jiangsu 213002, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Xingfu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ying
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Qing
authors.affiliation: Department of Geriatric Psychiatry, Wuxi Psychiatric Hospital, Nanjing Medical University, Wuxi, Jiangsu 214151, P.R. China.
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
authors.affiliation: Clinical Oncology Laboratory, Changzhou Cancer Hospital of Soochow University, Changzhou, Jiangsu 213002, P.R. China.
authors.forename: Changsong
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013406:Suicide, Attempted / Q000523:psychology*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase