Association study of neurotrophic tyrosine kinase receptor type 2 (NTRK2) and childhood-onset mood disorders
Association study of neurotrophic tyrosine kinase receptor type 2 (NTRK2) and childhood-onset mood disorders
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DOI：
10.1002/ajmg.b.30084
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发表时间：
2005-01-05
影响因子：
2.8
通讯作者：
Barr, CL
中科院分区：
文献类型：
--
作者：
Adams, JH;Wigg, KG;Barr, CL
儿童期发作的心境障碍（COMD）通常是家族性的，对COMD的双胞胎研究提供了令人信服的证据，表明遗传因素参与其中。神经可塑性的缺陷被认为是抑郁症发展的基础。受体原肌球蛋白相关激酶B（Trk B）及其配体脑源性神经营养因子（BDNF）在神经可塑性中起重要作用，这两种基因的mRNA表达已被证明受到应激和慢性抗抑郁治疗的影响。此外，TrkB基因敲除小鼠显示出不适当的压力应对机制。先前已经表明BDNF与COMD相关，在这项研究中，我们研究了编码TrkB的基因，神经营养酪氨酸激酶受体2（NTRK 2）作为COMD的易感因子。我们在两个独立样本中测试了NTRK 2与COMD的关联：（a）在种族和性别上匹配的病例对照样本，包括120例符合DSM III/IV标准的14岁之前的重度抑郁症或心境恶劣障碍或18岁之前的双相I/II型障碍的病例和对照，和（B）在匈牙利收集的113个家庭的基于家庭的对照样本，由7至14岁之间的先证者确定，符合DSM IV重度抑郁症或双相I/II障碍标准。在病例对照样本中，没有证据表明NTRK 2的三种多态性与COMD存在等位基因或基因型关联。同时，在以家庭为基础的样本中，使用传递不平衡。通过TDT测试，我们没有发现每个标记单独或当分析单倍型时等位基因关联的任何证据。基于这些结果，使用这三个多态性，我们没有发现支持NTRK 2作为COMD的易感基因。(C)2004 Wiley-Liss，Inc.
Childhood-onset mood disorders (COMD) are often familial, and twin studies of COMD provide compelling evidence that genetic factors are involved. Deficits in neural plasticity have been suggested to underlie the development of depression. The receptor tropomyosin related kinase B (TrkB) and its ligand, brain derived neurotrophic factor (BDNF), play essential roles in neural plasticity, and mRNA expression of both of these genes has been shown to be influenced by stress and chronic antidepressant treatment. In addition, TrkB, knockout mice display inappropriate stress coping mechanisms. Having previously shown that BDNF is associated with COMD, in this study we investigated the gene encoding TrkB, neurotrophic tyrosine kinase, receptor, type 2 (NTRK2) as a susceptibility factor in COMD. We tested for association of NTRK2 with COMD in two independent samples: (a) a case-control sample matched on ethnicity and gender, consisting of 120 cases who met DSM III/IV criteria for major depressive or dysthymic disorder before age 14 or bipolar I/II before the age of 18, and controls, and (b) a family based control sample of 113 families collected in Hungary, identified by a proband between the age of 7 and 14 who met DSM IV criteria for major depressive disorder or bipolar I/II disorder. There was no evidence for an allelic or genotypic association of three polymorphisms of NTRK2 with COMD in the case-control sample. Also, in the family based sample, using the transmission disequilibrium. test (TDT), we did not identify any evidence of allelic association for each marker individually or when haplotypes were analyzed. Based on these results, using these three polymorphisms, we do not find support for NTRK2 as a susceptibility gene for COMD. (C) 2004 Wiley-Liss, Inc.