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CeRNA network analysis and functional enrichment of salt sensitivity of blood pressure by weighted-gene co-expression analysis.

ABSTRACT: Background:Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. The pathogenic mechanisms of SSBP are still uncertain. This study aimed to construct the co-regulatory network of SSBP and data mining strategy based on the competitive endogenous RNA (ceRNA) theory. Methods:LncRNA and mRNA microarray was performed to screen for candidate RNAs. Four criteria were used to select the potential differently expressed RNAs. The weighted correlation network analysis (WGCNA) package of R software and target miRNA and mRNA prediction online databases were used to construct the ceRNA co-regulatory network and discover the pathways related to SSBP. Gene ontology enrichment, gene set enrichment analysis (GSEA) and KEGG pathway analysis were performed to explore the functions of hub genes in networks. Results:There were 274 lncRNAs and 36 mRNAs that differently expressed between salt-sensitive and salt-resistant groups (P < 0.05). Using WGCNA analysis, two modules were identified (blue and turquoise). The blue module had a positive relationship with salt-sensitivity (R = 0.7, P < 0.01), high-density lipoprotein (HDL) (R = 0.53, P = 0.02), and total cholesterol (TC) (R = 0.55, P = 0.01). The turquoise module was positively related with triglyceride (TG) (R = 0.8, P < 0.01) and low-density lipoprotein (LDL) (R = 0.54, P = 0.01). Furthermore, 84 ceRNA loops were identified and one loop may be of great importance for involving in pathogenesis of SSBP. KEGG analysis showed that differently expressed mRNAs were mostly enriched in the SSBP-related pathways. However, the enrichment results of GSEA were mainly focused on basic physical metabolic processes. Conclusion:The microarray data mining process based on WGCNA co-expression analysis had identified 84 ceRNA loops that closely related with known SSBP pathogenesis. The results of our study provide implications for further understanding of the pathogenesis of SSBP and facilitate the precise diagnosis and therapeutics.

SUBMITTER: Cao H

PROVIDER: S-EPMC6746216 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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CeRNA network analysis and functional enrichment of salt sensitivity of blood pressure by weighted-gene co-expression analysis.

Cao Han H Qi Han H Liu Zheng Z Peng Wen-Juan WJ Guo Chun-Yue CY Sun Yan-Yan YY Pao Christine C Xiang Yu-Tao YT Zhang Ling L

PeerJ 20190913

<h4>Background</h4>Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. The pathogenic mechanisms of SSBP are still uncertain. This study aimed to construct the co-regulatory network of SSBP and data mining strategy based on the competitive endogenous RNA (ceRNA) theory.<h4>Methods</h4>LncRNA and mRNA microarray was performed to screen for candidate RNAs. Four criteria were used to select the potential differently expressed RNAs. The weighted correl ...[more]

PMID: 31565555

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Project description:Background and aimsIdentify novel metabolite associations with blood pressure (BP) salt-sensitivity and hypertension.Methods and resultsThe Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Replication study includes 698 Chinese participants who underwent a 3-day baseline examination followed by a 7-day low-sodium feeding and 7-day high-sodium feeding. Latent mixture models identified three trajectories of blood pressure (BP) responses to the sodium interventions. We selected 50 most highly salt-sensitive and 50 most salt-resistant participants for untargeted metabolomics profiling. Multivariable adjusted mixed logistic regression models tested the associations of baseline metabolites with BP salt-sensitivity. Multivariable adjusted mixed linear regression models tested the associations of BP salt-sensitivity with metabolite changes during the sodium interventions. Identified metabolites were tested for associations with hypertension among 1249 Bogalusa Heart Study (BHS) participants using multiple logistic regression. Fifteen salt-sensitivity metabolites were associated with hypertension in the BHS. Baseline values of serine, 2-methylbutyrylcarnitine and isoleucine directly associated with high salt-sensitivity. Among them, serine indirectly associated with hypertension while 2-methylbutyrylcarnitine and isoleucine directly associated with hypertension. Baseline salt-sensitivity status predicted changes in 14 metabolites when switching to low-sodium or high-sodium interventions. Among them, glutamate, 1-carboxyethylvaline, 2-methylbutyrylcarnitine, 3-methoxytyramine sulfate, glucose, alpha-ketoglutarate, hexanoylcarnitine, gamma-glutamylisoleucine, gamma-glutamylleucine, and gamma-glutamylphenylalanine directly associated with hypertension. Conversely, serine, histidine, threonate and 5-methyluridine indirectly associated with hypertension. Together, these metabolites explained an additional 7% of hypertension susceptibility when added to a model including traditional risk factors.ConclusionsOur findings contribute to the molecular characterization of BP response to sodium and provide novel biological insights into salt-sensitive hypertension.

Dataset Information

CeRNA network analysis and functional enrichment of salt sensitivity of blood pressure by weighted-gene co-expression analysis.

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CeRNA network analysis and functional enrichment of salt sensitivity of blood pressure by weighted-gene co-expression analysis.

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