Chang Chuan-Chia, Lu Ru-Band, Chen Chih-Lun, Chu Chi-Ming, Chang Hsin-An, Huang Cheng-Chang, Huang Yi-Lin, Huang San-Yuan
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
J Psychiatry Neurosci. 2007 Mar;32(2):121-8.
Although the physiological mechanisms contributing to the development of major depression remain unclear, several lines of evidence suggest that the catecholaminergic system involving the norepinephrine transporter (NET) is implicated in the etiology of major depression. This study aims to determine whether major depression is associated with the NET gene in a Han Chinese population.
We analyzed the NET promoter T-182C polymorphism and another silent polymorphism G1287A in exon 9 of the NET gene with a polymerase chain reaction (PCR)-based method in 216 patients with major depression and 210 unrelated, age-and sex-matched healthy control subjects. We interviewed all subjects with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime; major depressive disorder was diagnosed according to DSM-IV criteria. In addition, to reduce the clinical heterogeneity, we performed a subtype analysis with clinically important variables, such as family history of major affective disorder and age at onset of major depression.
No significant difference was observed between the patients and healthy control subjects in the genotype distributions and allele frequencies for the investigated NET polymorphisms. Similarly, no significant differences were found between more homogeneous subgroups of patients and normal control subjects.
This study suggests that the investigated polymorphisms in the NET gene are not major risk factors in increasing susceptibility to either major depression or its clinical subtypes in a Han Chinese population. However, larger replication studies with different ethnic samples are needed.
尽管导致重度抑郁症发生的生理机制仍不明确,但有几条证据表明,涉及去甲肾上腺素转运体(NET)的儿茶酚胺能系统与重度抑郁症的病因有关。本研究旨在确定在汉族人群中重度抑郁症是否与NET基因相关。
我们采用基于聚合酶链反应(PCR)的方法,对216例重度抑郁症患者和210名年龄及性别匹配的无关健康对照者,分析NET基因启动子T-182C多态性以及外显子9中的另一个沉默多态性G1287A。我们用中文版修订版情感障碍与精神分裂症检查表对所有受试者进行访谈;根据《精神疾病诊断与统计手册》第四版标准诊断重度抑郁症。此外,为减少临床异质性,我们对具有临床重要变量(如重度情感障碍家族史和重度抑郁症发病年龄)进行了亚型分析。
在研究的NET多态性的基因型分布和等位基因频率方面,患者与健康对照者之间未观察到显著差异。同样,在患者和正常对照者更同质的亚组之间也未发现显著差异。
本研究表明,在汉族人群中,所研究的NET基因多态性不是增加患重度抑郁症或其临床亚型易感性的主要危险因素。然而,需要用不同种族样本进行更大规模的重复研究。