Association of the neurotrophic tyrosine kinase receptor 3 (NTRK3) gene and childhood-onset mood disorders
Association of the neurotrophic tyrosine kinase receptor 3 (NTRK3) gene and childhood-onset mood disorders
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DOI：
10.1176/appi.ajp.2007.07050805
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发表时间：
2008-05-01
影响因子：
17.7
通讯作者：
Barr, Cathy L.
中科院分区：
文献类型：
--
作者：
Feng, Yu;Vetro, Agnes;Barr, Cathy L.
目的：基因组扫描揭示了抑郁症与染色体15q25.3-q26.2连锁的重要证据。神经营养酪氨酸激酶受体3(NTRK3)是神经营养素-3(TrkC)的受体，也是神经营养因子信号转导的关键基因，位于该区域，有证据表明突触可塑性是情绪障碍的一种机制，被认为是首选候选基因。作者调查了NTRK3是儿童期情绪障碍的易感基因。方法：研究样本包括603个家庭，723个受影响的儿童和青少年，他们在15岁之前被诊断为首发情绪障碍。作者在这个样本中对NTRK3基因上的18个多态标记进行了基因分型，并进行了关联性检验。结果：利用传递不平衡检验，确定了5个标记存在关联的显著证据。5个标记中有4个位于强连锁不平衡区域，且高度相关。单倍型结果为由位于两个单倍型区块的标记组成的单倍型的关联提供了重要证据。结论：NTRK3的结果以及作者先前在该样本中发现的与脑源性神经营养因子关联的结果支持突触可塑性是导致儿童和青春期开始的情绪障碍的一种机制，并特别暗示NTRK3基因是15q链接区的一个贡献因素。
Objective: Genome scans have revealed significant evidence for linkage of depression to chromosome 15q25.3-q26.2. The gene for neurotrophic tyrosine kinase receptor 3 (NTRK3), the receptor for neurotrophin-3 (trkC) and a key gene in neurotrophin signaling, is located within this region and, given evidence for synaptic plasticity as a mechanism in mood disorders, was considered a prime candidate. The authors investigated NTRK3 as a susceptibility gene for childhood-onset mood disorders.Method: The study sample consisted of 603 families with 723 affected children and adolescents diagnosed with a mood disorder with onset of the first episode by age 15. The authors genotyped 18 polymorphic markers across the NTRK3 gene in this sample and tested for association.Results: Results identified significant evidence for association for five of the markers using the transmission disequilibrium test. Four of the five markers were located in a region of strong linkage disequilibrium and were highly correlated. Haplotype results provided significant evidence for association to haplotypes composed of markers located in two haplotype blocks.Conclusions: The results for NTRK3 as well as the authors' previous finding for association to brain-derived neurotrophic factor in this sample support synaptic plasticity as a mechanism contributing to mood disorders that begin during childhood and adolescence and specifically implicate the NTRK3 gene as a contributing factor in the 15q-linked region.