重性抑郁障碍NET基因多态性与静息态脑功能关联性研究

A association study of norepinephrine transporter(NET) gene polymorphism and A resting-state f MRI in major depressive disorder

目的本研究应用基因影像技术,探讨NET基因多态性(NET-rs28386840)对重性抑郁障碍静息态脑功能的影响。方法通过严格的纳入及排除标准选取56例重性抑郁障碍患者及22例健康对照,利用聚合酶链反应(PCR)和直接测序来检验NET基因rs28386840多态性及采用功能磁共振成像技术(f MRI),检测被试者静息状态下的自发脑功能活动,计算全脑低频振幅(ALFF)值,对结果进行两因素方差分析。结果 (1)主效应:疾病主效应:抑郁组较对照组ALFF值在右侧小脑后叶、左侧小脑后叶、右侧梭状回、右侧枕中回降低,在左侧颞中回、左侧缘上回升高;基因主效应:T等位基因携带组较A等位基因携带组ALFF值在右侧小脑后叶、右侧梭状回、右侧颞中回降低。(2)交互作用:病例组较对照组,T等位基因携带者较A等位基因携带者ALFF值在右侧眶部额中回,左侧枕中回降低,在左侧海马旁回、右侧小脑升高。结论重性抑郁障碍NET基因rs28386840多态性与静息状态下部分脑区功能异常有关,且与是否患病存在交互作用。

Objective This study applies gene imaging technology, to investigate the NET gene polymorphism （NET-rs28386840） which effects on resting-state fMRI with major depressive disorder. Methods Through strict inclusion and exclusion criteria to select 56 patients with MDD and 22 healthy control. Polymerase chain reaction （PCR） and DNA sequencing analysis were used to detect the genotype of NET-rs28386840 gene single nucleotide polymorphisms （SNP）. Using functional magnetic resonance imaging （fMRI）, test subjects brain activity on resting-state. ALFF analysis were used to detect neural spontaneous activity across the whole brain by REST, two-factor analysis of variance was performed by SPM5. Results Main effect： the diseased main effect： compared with healthy control group, patients group showed decreased ALFF in the Right Cerebellum Posterior Lobe, Right Cerebellum Anterior Lobe, Fusiform_R（aal）, Occipital_Mid_R（aal）, and increased ALFF in the Temporal_Mid_L（aal）, Supra Marginal_L（aal）. The gene main effect： compared with ＂A＂ alleles carried, ＂T＂ alleles carried showed decreased ALFF in the Right Cerebellum Posterior Lobe, Fusiform_R（aal）, Temporal_Mid_R（aal）. Interaction： the interaction depression with gene polymorphism was showed, compared with healthy control group to patients group, the ALFF decreased in the Frontal_Mid_Orb_R（aal）, Occipital_Mid_L（aal） and increased in the Para Hippocampal_L（aal）, Right Cerebellum, by ＂A＂ alleles carried comparing ＂T＂alleles carried. Conclusion NET-Rs28386840 gene polymorphism and the resting-state function of some brain regions are abnormal with major depressive disorder, and have interaction with diseased, so we speculate that the NET gene play an important role in the pathogenesis of depression.