The Gender-Specific Interaction of DVL3 and GSK3β Polymorphisms on Major Depressive Disorder Susceptibility in a Chinese Han Population: A Case-Control Study.

Siyuan Ke,Zhengxue Qiao,Wenxin Zhang,Jiarun Yang,Yanjie Yang,Xuan Liu,Xiaohui Qiu,Xueyan Zhao,Jiawei Zhou,Tianyi Bu,Xiuxian Yang,Lu Zhao,Xiongzhao Zhu,Jiarui Li,Yuying Tong,Fushun Wang

doi:10.1155/2022/2633127

Abstract

Based on the “oxidative stress hypothesis” of major depressive disorder (MDD), cells regulate their structure through the Wnt pathway. Little is known regarding the interactions of dishevelled 3 (DVL3) and glycogen synthase kinase 3 beta (GSK3β) polymorphisms with MDD. The aim of the current study was to verify the relationship between DVL3 and GSK3β genetic variants in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity. A total of 1136 participants, consisting of 541 MDD patients and 595 healthy subjects, were recruited. Five single-nucleotide polymorphisms (SNPs) of DVL3/GSK3β were selected to assess their interaction by use of a generalized multifactor dimensionality reduction method. The genotype and haplotype frequencies of DVL3/GSK3β polymorphisms were significantly different between patients and controls for DVL3 rs1709642 (P < 0.01) and GSK3β rs334558, rs6438552, and rs2199503 (P < 0.01). In addition, our results also showed that there were significant interaction effects between DVL3 and GSK3β polymorphisms and the risk of developing MDD, particularly in women. The interaction between DVL3 (rs1709642) and GSK3β (rs334558, rs6438552) showed a cross-validation (CV) consistency of 10/10, a P value of 0.001, and a testing accuracy of 59.22%, which was considered as the best generalized multifactor dimensionality reduction (GMDR) model. This study reveals the interaction between DVL3 and GSK3β polymorphisms on MDD susceptibility in a female Chinese Han population. The effect of gender should be taken into account in future studies that seek to explore the genetic predisposition to MDD relative to the DVL3 and GSK3β genes.

Highlights

Major depressive disorder (MDD) is a common mental disorder, afflicting more than 300 million people globally [1]
We investigated the relationship between dishevelled 3 (DVL3)/GSK3β polymorphisms and MDD risk in a Chinese Han population
Our results showed that a dominant model of inheritance was a better fit for the association between MDD and DVL3/GSK3β polymorphisms

Summary

Introduction

Major depressive disorder (MDD) is a common mental disorder, afflicting more than 300 million people globally [1]. As matters stand, the diagnostic capacity and efficacy of predicting the risk for developing MDD is still suboptimal. This is mostly because the pathophysiology of MDD is not entirely clear. Preclinical and clinical studies have shown that increased generation of ROS (reactive oxygen species, ROS) and exhaustion of antioxidative defences are responsible for the altered brain structure. This hypothesis is known as the “oxidative stress hypothesis” of MDD [4]

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