抑郁症患者SIRT1基因rs3740051位点基因多态性与脑灰质关系的研究

Correlation between rs3740051 polymorphism of SIRT1 gene and volume of brain gray matter in depression patients

目的研究首发未治疗抑郁症患者SIRT1基因rs3740051基因多态性与脑灰质结构之间的关系。方法选取2018年3月至2019年9月陆军军医大学第一附属医院医学心理科门诊抑郁症患者75例,招募健康对照43例,使用磁共振采集高分辨率结构像数据,并对SIRT1基因rs340051位点进行基因分型测序,根据分型结果将抑郁症患者组和健康对照组进一步分为4组:抑郁(AA)组、抑郁(AG/GG)组、对照(AA)组和对照(AG/GG)组,分析SIRT1基因rs3740051位点基因型(AA和AG/GG)与疾病诊断(抑郁和对照)对于大脑灰质体积交互效应和各自主效应。结果①4组大脑灰质体积存在诊断和基因型交互效应,在左侧海马旁回和左侧顶下缘角回,抑郁(AG/GG)组灰质体积大于抑郁(AA)组(P<0.05),对照(AA)组灰质体积大于对照(AG/GG)组(P<0.05)。②4组大脑灰质体积存在诊断主效应,在左侧顶下缘角回,对照(AA)组与抑郁(AA)组差异无统计学意义,抑郁(AG/GG)组灰质体积大于对照(AG/GG)组(P<0.05),在右侧楔前叶,抑郁(AG/GG)组灰质体积大于对照组(AG/GG)(P<0.05),抑郁(AA)组灰质体积大于对照(AA)组(P<0.05)。③4组大脑灰质体积存在基因型主效应,在右侧内侧额上回和左侧补充运动区区域,对照(AG/GG)组灰质体积大于对照(AA)组(P<0.05),抑郁(AG/GG)组灰质体积大于抑郁(AA)组(P<0.05)。结论SIRT1基因rs3740051位点基因多态性位点可能与抑郁症患者大脑灰质体积的改变有关,携带G等位基因(AG/GG)相对于不携带G等位基因(AA)对于抑郁症大脑灰质体积改变更大,该改变可能在抑郁症发病机制中发挥作用。

Objective To investigate the correlation between the polymorphism of SIRT1 locus rs3740051 and the structure of brain gray matter in patients with first-onset untreated depression as well as in healthy controls.Methods Clinical data of 75 patients(15 males and 60 females)with first-onset depression treated in our hospital from March 2018 to September 2019 were recruited,and another 43 volunteers were enrolled as healthy controls.Their brain structural data were collected from high resolution images after magnetic resonance imaging,and the allelic and genotypic frequencies of rs3740051 polymorphisms of SIRT1 gene were determined with DNA sequencing in the 2 groups.Based on the detected genotypes,the depression patients and healthy controls were classified into 4 groups:depression(AA),depression(AG/GG),control(AA)and control(AG/GG)groups.The interaction effects of SIRT1 rs3740051 genotypes(AA or AG/GG)and disease diagnosis(depression or control),as well as their respective main effects on brain gray matter,on brain gray matter volume were analyzed.Results①Diagnostic and genotype interaction effects on the gray matter volume were shown in all the 4 groups.In the left parahippocampal gyrus and left inferior parietal marginal angular gyrus,the gray matter volume was larger in the depression(AG/GG)group than depression(AA)group(P<0.05),and larger in the control(AA)group than control(AG/GG)group(P<0.05).②Diagnostic main effects on the gray matter volume existed in all the 4 groups.In the left inferior parietal marginal angular gyrus,the gray matter volume of the depression(AG/GG)group was greater than that of control(AG/GG)group(P<0.05),though the depression(AA)group and control(AA)group showed no significant difference(P>0.05).At the right precuneus,the gray matter volume was larger in both depression(AG/GG)and depression(AA)groups as compared with the corresponding control groups(P<0.05).③Genotype main effects were also found on gray matter volume of the 4 groups.In the right medial superior frontal gyrus and left supplementary motor area,the gray matter volume was larger in both depression(AG/GG)and control(AG/GG)groups than the corresponding(AA)genotype groups(P<0.05).Conclusion The polymorphism of SIRT1 rs3740051 may be related to the alteration of brain gray matter volume in patients with depression.Patients carrying G allele(AG/GG)have more changes in gray matter volume than those not carrying(AA),and these changes may play a role in the pathogenesis of depression.