Feng Yu, Vetró Agnes, Kiss Eniko, Kapornai Krisztina, Daróczi Gabriella, Mayer László, Tamás Zsuzsanna, Baji Ildikó, Gádoros Júlia, King Nicole, Kennedy James L, Wigg Karen, Kovacs Maria, Barr Cathy L
Toronto Western Research Institute, University Health Network, Toronto, Ont., Canada M5T 2S8.
Am J Psychiatry. 2008 May;165(5):610-6. doi: 10.1176/appi.ajp.2007.07050805. Epub 2008 Mar 17.
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.
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 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.
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.
基因组扫描已揭示出抑郁症与15号染色体q25.3 - q26.2区域存在显著的连锁证据。神经营养性酪氨酸激酶受体3（NTRK3）基因，即神经营养因子-3（trkC）的受体，是神经营养因子信号传导中的关键基因，位于该区域内，鉴于突触可塑性作为情绪障碍发病机制的证据，它被视为主要候选基因。作者研究了NTRK3作为儿童期起病情绪障碍的易感基因。
研究样本包括603个家庭，其中有723名受影响的儿童和青少年，他们被诊断为情绪障碍，首次发作年龄在15岁之前。作者对该样本中NTRK3基因的18个多态性标记进行基因分型并检测关联性。
使用传递不平衡检验，结果确定了5个标记存在显著的关联证据。5个标记中的4个位于强连锁不平衡区域且高度相关。单倍型结果为与由位于两个单倍型块中的标记组成的单倍型存在关联提供了显著证据。
NTRK3的研究结果以及作者之前在该样本中发现的与脑源性神经营养因子的关联，支持突触可塑性作为导致儿童期和青少年期起病的情绪障碍的一种机制，并且特别表明NTRK3基因是15q连锁区域中的一个促成因素。
