Bioinformatics analysis of regulatory network of long non-coding RNA LOC107987438 in depressive disorder / 中华行为医学与脑科学杂志

Objective:To investigate the regulatory role of defferentially expressed LOC107987438 in the pathogenesis of depressive disorder and provide a theoretical basis for its clinical application in depressive disorder.Methods:Differential expression of LOC107987438 was verified by quantitative real-time polymerase chain reaction(qRT-PCR)in peripheral blood monocular cells(PBMCs)of 60 patients with depressive disorder and 60 health controls. In addition, its diagnostic value was assessed by receiver operating characteristic(ROC)curves. Based on the ceRNA mechanism of lncRNA, the miRDB database was applied to predict the target miRNAs of LOC107987438, and the miRNAs with target score ≥ 80 among them were screened out.The screened miRNAs were then used to predict their potential target mRNAs through four databases which were TargetScan 8.0, miRTarBase, mirDIP and miRPathDB. Moreover, the predicted target mRNAs were annotated for gene ontology(GO)function annotation and tokoyo encyclopedia of genes and genomes(KEGG) pathway enrichment analysis via ClusterProfiler 4.0.5 package of R 4.1.1. Finally, a protein-protein interaction network was constructed using the STRING 11.5 platform to retrieve the interacting genes.Results:The qRT-PCR results showed that normalized expression of LOC107987438 in PBMCs of patients with depressive disorder was higher than that in health controls(depressive disorder: 2.084±1.357, health controls: 1.000±0.660, P<0.001). The ROC curve results showed that the area under curves(AUC)of LOC107987438 was 0.759(95% CI: 0.675-0.842, P<0.05), indicating its high potential diagnostic value. Bioinformatics analysis showed that hsa-miR-4670-3p, hsa-miR-619-3p, hsa-miR-6721-5p and hsa-miR-297 were the miRNAs with high bindings to LOC107987438. The results of KEGG signaling pathway enrichment revealed that hypoxia-inducible factor 1(HIF-1)signaling pathway, phosphatidylinositol 3-kinase-AKT(PI3K-Akt) signaling pathway and erythroblastic oncogene B(ErbB) signaling pathway were closely associated with depressive disorder. Among the top ten key genes screened by the protein-protein interaction network, kirsten rats arcomaviral oncogene homolog(KRAS), androgen receptor(AR), cyclic-AMP response binding protein1(CREB1), insulin-like growth factor 1(IGF1), cyclin-dependent kinase inhibitor 1B(CDKN1B) and calcium/calmodulin-dependent protein kinase type Ⅱ alpha(CAMK2A)were strongly associated with depressive disorder. Conclusion:The establishment of ceRNA regulatory network of LOC107987438 provides a theoretical basis for exploring the pathophysiology of depressive disorders.

Association study of interaction of tryptophan hydroxylase 2 with serotonin 1A receptor gene polymorphism on major depressive disorder / 中华行为医学与脑科学杂志

Objective To explore the interaction between tryptophan hydroxylase 2(TPH2) gene polymorphisms (rs4570625,rs11178997) and serotonin 1A receptor (5-HT1A) gene polymorpbisms (rs878567,rs1364043,rs6265) and the association with major depressive disorder (MDD) in a Chinese Han population.Methods The DNA isolated from peripheral blood samples of 288 MDD patients 288 healthy subjects was detected by single base primer extension assay (Snapshot).The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction.Results Significant differences were found in the genotype (patients (TT:27,TA:152,AA:109),controls (TT:82,TA:105,AA:101),P＜0.01) and allele(patients (T:206,A:370),controls (T:269,A:307),P＜0.01) frequencies of rs1 1178997 within TPH2 between MDD patients and controls.Statistically,a greater risk of developing MDD was found in individuals with an rs1 1178997 A-allele(OR=1.574,95％CI=1.243-1.993).The interaction between TPH2 (rs4570625,rs1 1178997) and 5-HT1A (rs878567,rs1364043,rs6265) was considered as the best multi-locus model,and this showed a testing accuracy of 57.67％ and a CV consistency of 10/10.And this interaction had a significant effect on the risk of MDD (P=0.0107).Conclusion There may be an association between the interaction of TPH2 and 5-HT1A polymorphisms and MDD.

Interaction of GNβ3 gene polymorphisms and environmental factors in susceptibility to major depressive disorder / 中华行为医学与脑科学杂志

Objective To explore the association between GNβ3 gene and depression,and to investigate the interaction of gene-environment(negative life events and childhood trauma) and potential possible pathogenesis of depression.Methods The sample of peripheral blood was collected from Chinese Northern patients(n=500) and controls(n=500).Snapshot technique was used to detect the genotype frequency and allele frequency of GNβ3 rs5443 polymorphism in cases and controls.The genotype and allele frequencies were analyzed by Chi-square test,the interactions of gene-environment were analyzed by Logistic regression.Results GNβ3 rs5443 genotype and allele frequencies were observed between patients and controls (x2 =20.249,P＜0.01;x2 =4.803,P＜0.05).There were genotype CC 102 and 158,genotype CT 280 and 217,genotype TT 118 and 125;allele C 484 and 533,allele T 516 and 467 between patients and controls,respectively.Logistic regression analysis showed that the interaction between rs5443 T+ and negative life events was associated with depression (P＜0.05,OR=1.957).In addition,individual carrying rs5443T+ genotypes and negative life events could increase risk of depression.Conclusion GNβ3 rs5443 is a possible susceptibility gene of depression.The interaction between rs5443 and negative life events is associated with depression.