Association of Apelin and Apelin Receptor Polymorphisms With the Risk of Comorbid Depression and Anxiety in Coronary Heart Disease Patients

Wang, Ying; Liu, Wenhui; Yu, Xiao; Yuan, Haiyan; Wang, Feng; Jiang, Pei; Luo, Zhicheng

doi:10.3389/fgene.2020.00893

Cited by 8 publications

(3 citation statements)

References 36 publications

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“…Meanwhile, the downstream pathway of hsa-miR-130a contained apelin signaling pathway, which was associated with cardiovascular disorders, and had been suggested to be a candidate pathway for the development of coronary heart disease, depression, and anxiety disorders. [ 82 ] In the results of molecular docks, β-sitosterol, stigmasterol, cryptotanshinone, and cavidine all showed good docking affinity (affinity < –7 kcal/mol) with TP53. The β-sitosterol and stigmasterol also showed good affinity with FOS.…”

Section: Discussionmentioning

confidence: 99%

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study

Liu,

Sun,

Bao

et al. 2024

Medicine

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The purpose of this study is to investigate the potential mechanisms of Chinese herbs for the treatment of insomnia using a combination of data mining, network pharmacology, and molecular-docking validation. All the prescriptions for insomnia treated by the academician Qi Wang from 2020 to 2022 were collected. The Ancient and Modern Medical Case Cloud Platform v2.3 was used to identify high-frequency Chinese medicinal herbs and the core prescription. The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were utilized to predict the effective active components and targets of the core herbs. Insomnia-related targets were collected from 4 databases. The intersecting targets were utilized to build a protein–protein interaction network and conduct gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the STRING database, Cytoscape software, and clusterProfiler package. Gene chip data (GSE208668) were obtained from the Gene Expression Omnibus database. The limma package was applied to identify differentially expressed genes (DEGs) between insomnia patients and healthy controls. To create a “transcription factor (TF)-miRNA-mRNA” network, the differentially expressed miRNAs were entered into the TransmiR, FunRich, Targetscan, and miRDB databases. Subsequently, the overlapping targets were validated using the DEGs, and further validations were conducted through molecular docking and molecular dynamics simulations. Among the 117 prescriptions, 65 herbs and a core prescription were identified. Network pharmacology and bioinformatics analysis revealed that active components such as β-sitosterol, stigmasterol, and canadine acted on hub targets, including interleukin-6, caspase-3, and hypoxia-inducible factor-1α. In GSE208668, 6417 DEGs and 7 differentially expressed miRNAs were identified. A “TF-miRNA-mRNA” network was constructed by 4 “TF-miRNA” interaction pairs and 66 “miRNA-mRNA” interaction pairs. Downstream mRNAs exert therapeutic effects on insomnia by regulating circadian rhythm. Molecular-docking analyses demonstrated good docking between core components and hub targets. Molecular dynamics simulation displayed the strong stability of the complex formed by small molecule and target. The core prescription by the academician Qi Wang for treating insomnia, which involves multiple components, targets, and pathways, showed the potential to improve sleep, providing a basis for clinical treatment of insomnia.

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Section: Discussionmentioning

confidence: 99%

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study

Liu,

Sun,

Bao

et al. 2024

Medicine

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“…In the cardiovascular system apelin-APLNR pathway plays a central role, and circulating apelin is a promising CHD predictor [40]. Wang et al [41] conducted a case-control study of 269 patients with CHD (122 of them suffering from depression) and 184 healthy people in China. It is the rst report that after adjusting drinking habits, insomnia, hypertension, and stroke history, patients with CHD who carry the APLNR rs9943582 C allele still have a higher risk of depression.…”

Section: -Ht Transporter(5-httmentioning

confidence: 99%

The Effect of Single Nucleotide Polymorphisms on Depression in Combination With Coronary Diseases: Protocol for a Systematic Review and Meta-analysis

Dz¹,

Gao²,

H³

et al. 2021

Preprint

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Background: Depression and coronary heart disease (CHD) have common risk mechanisms. Common single nucleotide polymorphisms (SNPs) may be associated with the risk of depression combined with coronary heart disease. Methods: This protocol was designed according to the PRISMA-P guidelines. CENTRAL in the Cochrane Library, MEDLINE Ovid, Embase Ovid, Web of Science, CNKI, CQVIP, SinoMed, Wanfang Data, and ChiCTR will be systematically searched. We will include case-control studies and cohort studies investigating the relationship between gene SNPs and depression and coronary heart disease comorbidities. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias. When measuring dichotomous outcomes, we will use the risk ratio (RR) and 95% confidence interval (95%CIs) in a cohort study and use the odds ratio (OR) and 95% confidence interval (95%CIs) in a case-control study. Five genetic models (allele model, homozygous model, heterozygous model, dominant model, and recessive model) will be evaluated for each included study. Subgroup analysis by ethnicity will be performed. If necessary, post hoc analysis will be made according to different types.Discussion: The purpose of this meta-analysis is to comprehensively study the current evidence and assess the association between single nucleotide polymorphisms and susceptibility of depression in combination with coronary heart disease.Systematic review registration: This protocol was prospectively registered in the PROSPERO (registration number CRD42021229371).

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“…In the cardiovascular system, the apelin-APLNR pathway plays a central role, and circulating apelin is a promising CHD predictor (40). Wang et al (41) conducted a case-control study of 269 patients with CHD (122 of them suffering from depression) and 184 healthy people in China. It is the first report that after adjusting drinking habits, insomnia, hypertension, and stroke history, patients with CHD who carry the APLNR rs9943582 C allele still have a higher risk of depression.…”

Section: Introductionmentioning

confidence: 99%

The effect of single nucleotide polymorphisms on depression in combination with coronary diseases: a systematic review and meta-analysis

Zhang,

Gao,

Yang

et al. 2024

Front. Endocrinol.

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BackgroundDepression and coronary heart disease (CHD) have common risk mechanisms. Common single nucleotide polymorphisms (SNPs) may be associated with the risk of depression combined with coronary heart disease.MethodsThis study was designed according to the PRISMA-P guidelines. We will include case-control studies and cohort studies investigating the relationship between gene SNPs and depression and coronary heart disease comorbidities. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias. When measuring dichotomous outcomes, we will use the odds ratio (OR) and 95% confidence interval (95%CIs) in a case-control study. Five genetic models (allele model, homozygous model, co-dominant model, dominant model, and recessive model) will be evaluated for each included study. Subgroup analysis by ethnicity will be performed. If necessary, post hoc analysis will be made according to different types.ResultsA total of 13 studies were included in this study, and the types of genes included are FKBP5 and SGK1 genes that act on glucocorticoid; miR-146a, IL-4-589, IL-6-174, TNF-α-308, CRP-717 genes that act on inflammatory mechanisms; eNOS genes from endothelial cells; HSP70 genes that act on the autoimmune response; ACE2 and MAS1 genes that act to mediate Ang(1-7) in the RAS system; 5-HTTLPR gene responsible for the transport of serotonin 5-HT and neurotrophic factor BDNF gene. There were three studies on 5-HTTLPR and BDNF genes, respectively, while there was only one study targeting FKBP5, SGK1, miR-146a, IL-4-589, IL-6-174, TNF-alpha-308, CRP-717, eNOS, HSP70, ACE2, and MAS1 genes. We did not perform a meta-analysis for genes reported in a single study, and meta-analysis was performed separately for studies exploring the 5-HTTLPR and BDNF genes. The results showed that for the 5-HTTLPR gene, there was a statistically significant association between 5-HTTLPR gene polymorphisms and depression in combination with coronary diseases (CHD-D) under the co-dominant model (LS vs LL: OR 1.76, 95%CI 1.20-2.59; SS vs LL: OR 2.80, 95%CI 1.45 to 5.41), the dominant model (LS+SS vs LL: OR 2.06, 95%CI 1.44 to 2.96), and the homozygous model (SS vs LL: OR 2.80 95%CI 1.45 to 5.5.41) were statistically significant for CHD-D, demonstrating that polymorphisms in the 5-HTTLPR gene are associated with the development of CHD-D and that the S allele in the 5-HTTLPR gene is likely to be a risk factor for CHD-D. For the BDNF gene, there were no significant differences between one of the co-dominant gene models (AA vs GG: OR 6.63, 95%CI 1.44 to 30.64), the homozygous gene model (AA vs GG: OR 6.63,95% CI 1.44 to 30.64), the dominant gene model (GA+AA vs GG: OR4.29, 95%CI 1.05 to 17.45), recessive gene model (AA vs GG+GA: OR 2.71, 95%CI 1.16 to 6.31), and allele model (A vs G: OR 2.59, 95%CI 1.18 to 5.67) were statistically significant for CHD-D, demonstrating that BDNFrs6265 gene polymorphisms are associated with the CHD-D development and that the A allele in the BDNFrs6265 gene is likely to be a risk factor for CHD-D. We analyzed the allele frequencies of SNPs reported in a single study and found that the SNPs in the microRNA146a gene rs2910164, the SNPs in the ACE2 gene rs2285666 and the SNPs in the SGK1 gene rs1743963 and rs1763509 were risk factors for the development of CHD-D. We performed a subgroup analysis of three studies involving the BDNFrs6265 gene. The results showed that European populations were more at risk of developing CHD-D than Asian populations in both dominant model (GA+AA vs GG: OR 10.47, 95%CI 3.53 to 31.08) and co-dominant model (GA vs GG: OR 6.40, 95%CI 1.98 to 20.73), with statistically significant differences. In contrast, the studies involving the 5-HTTLPR gene were all Asian populations, so subgroup analyses were not performed. We performed sensitivity analyses of studies exploring the 5-HTTLPR and BDNF rs6265 genes. The results showed that the results of the allele model, the dominant model, the recessive model, the homozygous model and the co-dominant model for both 5-HTTLPR and BDNF rs6265 genes were stable. Due to the limited number of studies of the 5-HTTLPR and BDNF genes, it was not possible to determine the symmetry of the funnel plot using Begg’s funnel plot and Egger’s test. Therefore, we did not assess publication bias.DiscussionSNPs of the microRNA146a gene at rs2910164, the ACE2 gene at the rs2285666 and the SGK1 gene at rs1743963 and rs1763509, and the SNPs at the 5-HTTLPR and BDNF gene loci are associated with the onset of comorbid depression in coronary heart disease. We recommend that future research focus on studying SNPs’ impact on comorbid depression in coronary heart disease, specifically targeting the 5-HTTLPR and BDNF gene at rs6265.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021229371.

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Association of Apelin and Apelin Receptor Polymorphisms With the Risk of Comorbid Depression and Anxiety in Coronary Heart Disease Patients

Cited by 8 publications

References 36 publications

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study

The Effect of Single Nucleotide Polymorphisms on Depression in Combination With Coronary Diseases: Protocol for a Systematic Review and Meta-analysis

The effect of single nucleotide polymorphisms on depression in combination with coronary diseases: a systematic review and meta-analysis

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