Mann J John, Currier Dianne, Murphy Lauren, Huang Yung-yu, Galfalvy Hanga, Brent David, Greenhill Laurence, Oquendo Maria
Department of Neuroscience, New York State Psychiatric Institute, NY 10032, USA.
J Affect Disord. 2008 Feb;106(1-2):117-21. doi: 10.1016/j.jad.2007.05.031. Epub 2007 Jul 2.
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. TPH2 is a recently discovered isoform that is expressed predominantly in serotonin neurons. Associations are reported of TPH2 polymorphisms with MDD, bipolar disorder and suicidal behavior. This study examines a single nucleotide polymorphism in the putative promoter region of the TPH2 gene.
One hundred nine bipolar, 324 major depressive disorder, and 130 healthy volunteers were genotyped for the rs4131347 (-C8347G) promoter SNP. Association was assessed with diagnosis, suicide attempt status, severity of psychopathology and cerebrospinal fluid monoamine metabolite levels of 5-HIAA, HVA, and MHPG. General linear models and logistic regression tested the effect of genotype*childhood abuse interactions on psychopathology severity and suicide attempt.
There was no association between genotype and either mood disorder, suicide attempt status, psychopathology severity or CSF monoamine metabolite levels.
No association was detected between the rs4131347 (-C8347G) SNP in the promoter region of the TPH2 gene and mood disorders, suicidal behavior or monoamine function.
色氨酸羟化酶(TPH)是5-羟色胺合成中的限速酶。TPH2是最近发现的一种亚型,主要在5-羟色胺能神经元中表达。有报道称TPH2基因多态性与重度抑郁症、双相情感障碍及自杀行为有关。本研究检测了TPH2基因假定启动子区域的一个单核苷酸多态性。
对109例双相情感障碍患者、324例重度抑郁症患者及130名健康志愿者进行rs4131347(-C8347G)启动子单核苷酸多态性基因分型。评估其与诊断、自杀未遂状态、精神病理学严重程度以及脑脊液中5-羟吲哚乙酸(5-HIAA)、高香草酸(HVA)和3-甲氧基-4-羟基苯乙二醇(MHPG)单胺代谢物水平的相关性。采用一般线性模型和逻辑回归分析基因型*童年期虐待交互作用对精神病理学严重程度和自杀未遂的影响。
基因型与心境障碍、自杀未遂状态、精神病理学严重程度或脑脊液单胺代谢物水平之间均无相关性。
未检测到TPH2基因启动子区域的rs4131347(-C8347G)单核苷酸多态性与心境障碍、自杀行为或单胺功能之间存在关联。