Dvl3 polymorphism interacts with life events and pro-inflammatory cytokines to influence major depressive disorder susceptibility

Jian Zhang,Xiongzhao Zhu,Xiongzhao Zhu,Yanjie Yang,Dong Han,Jingsong Ma,Jiarun Yang,Depin Cao,Xueyan Zhao,Bo Ban,Xiaohui Qiu

doi:10.1038/s41598-018-31530-2

Abstract

The purpose of this study is to explore Dvl3 variants and their interaction with negative life events on MDD susceptibility in a Chinese Han population. Additionally, we also attempted to identify whether there is an association between Dvl3 variants and pro-inflammatory cytokines. A total of 1102 participants, consisting of 550 patients with MDD and 552 healthy subjects, were recruited for genotyping by TaqMan allelic discrimination assay. Pro-inflammatory cytokine mRNA levels in peripheral blood were measured by QPCR. After the assessment of negative life events by the Life Events Scale, the Dvl3 gene–environment interaction (G × E) and risk factors were evaluated using generalized multifactor dimensionality reduction method (GMDR) and logistic regression analysis, respectively. This study is the first to reveal the interaction between Dvl3 allelic variations and negative life events as well as pro-inflammatory cytokines on MDD susceptibility in a Chinese Han population.

Highlights

Major depressive disorder (MDD), as a severe psychiatric disorder featured by persistent low mood, has a serious effect on physical and psychological health in humans
It codes for the disheveled segment polarity protein (Dvl)-3, which takes part in the wingless-related integration site (Wnt) signaling pathway, which is crucial for regulation of hippocampal neurogenesis[5]
We conducted a case-control study to ascertain whether Dvl[3] polymorphisms and negative life events as well as their interactions were associated with MDD among northern Chinese Han population

Summary

Introduction

Major depressive disorder (MDD), as a severe psychiatric disorder featured by persistent low mood, has a serious effect on physical and psychological health in humans. Studies on etiology of MDD have illustrated the gene–environment (G × E) interaction of certain risk genes and negative life events was associated with considerably greater risk of developing mood disorders. Over the past several decades, there has been strong and wide support for the cytokine hypothesis, a general hypothesis based on immune–inflammatory system dysfunction It is one of the more prevalent theories concerning MDD and might provide insights into the pathogenesis of depression and development of biomarkers and, more effective depression therapies. We conducted a case-control study to ascertain whether Dvl[3] polymorphisms and negative life events as well as their interactions were associated with MDD among northern Chinese Han population. Considering that the etiology of depression is associated with stress, we analyzed inflammatory cytokine production in peripheral blood in patients with MDD and discussed the potential connection between inflammatory cytokines and MDD

Objectives

Methods

Results

Discussion

Conclusion