Association of EGF, IGFBP-3 and TP53 Gene Polymorphisms with Major Depressive Disorder in Slovak Population

Abstract

SUMMARYBackground: Major depressive disorder (MDD) is a main public health concern worldwide. Despite extensive investigations, the exact mechanisms responsible for MDD have not been identified. Epidermal growth factor (EGF) and insulin growth factor binding protein-3 (IGFBP-3) are involved in brain function. Tumour suppressor protein p53 is widely involved in neuronal death in response to different forms of acute insults and neurological disorders. The present study focuses on the possible associations of the single-nucleotide polymorphisms (SNP) of EGF A61G (rs4444903), IGFBP-3 C32G (rs2854746) and TP53 G72C (rs1042522) genes with MDD risk in the Slovak population.Methods: The present case-control association study was carried out in 111 confirmed MDD patients and 207 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods.Results: Logistic regression analysis showed no association between SNPs of selected genes and MDD risk in the Slovak population. However, the stratification of individuals by gender revealed that males carrying IGFBP-3 G alleles (G32G or GG) had marginally increased risk for developing MDD as compared to CC homozygous males (p = 0.09). In women, inverse association was observed between SNP rs1042522 and MDD risk (p = 0.04 for recessive model).Conclusion: Our results suggest the protective effect of minor allele 72C of TP53 gene towards MDD. The disruption of mechanisms involved in cell survival and death regulation may be involved in pathophysiology of MDD.

A Novel Network Pharmacology Strategy to Decode Metabolic Biomarkers and Targets Interactions for Depression

“…The minor allele 72C of the tumor protein P53 (TP53) gene plays a protective role in the occurrence of depression. It participates in the pathological mechanism of depression through the cell survival and death regulation ( 42 ). Previous studies have reported that proinflammatory cytokines such as IL-1 beta (IL1B) ( 43 ) and tumor necrosis factor (TNF) ( 44 ) have been implicated in the pathogenesis molecular mechanism of depression.…”

Identification of potential Mitogen-Activated Protein Kinase-related key genes and regulation networks in molecular subtypes of major depressive disorder

“…TP53 mutation is also an independent risk factor for immune escape (34). Though some reports noted that the mechanisms involved in cell survival and death regulation based on TP53 might be interested in the pathophysiology of MDD (35), there is no more indication about TP53 and MDD. To some extent, we inspired a new light on the association between the traditional molecule and MDD.…”

Transcriptomic Signaling Pathways involved in a naturalistic model of Inflammation-related Depression and its remission

“…For example, a transcriptomic analysis of postmortem prefrontal cortex tissues from patients with a history of MDD revealed altered expression of apoptosis factors together with increased cytokines expression [26]. The importance of TP53 pathway itself was described in an animal model of trauma by transcriptional analysis from blood, amygdala and hippocampus [27] and in a genetic study where polymorphisms within TP53 gene were found associated with MDD in a Slovak population [28]. Interestingly, TP53 was also shown to be increased in the adipose tissue of obese mice and responsible for cytokine production and senescence-like changes thereby contributing to insulin resistance [29].…”