Genomic and RNA-Seq profiling of patients with HFrEF unraveled OAS1 mutation and aggressive expression. (15th March 2023)

• Record Type: Journal Article
• Authors: Li, Xin; Shen, Yanying; Xu, Xiang; Guo, Ge; Chen, Yibing; Wei, Qingxia; Li, Hanlu; He, Kunlun; Liu, Chunlei
• Is Part Of: International journal of cardiology. Volume 375(2023)
• Page Start: 44
• Page End: 54
• Publication Date: 2023-03-15
• Subjects: HF heart failure -- HFrEF heart failure with reduced ejection fraction -- HCM hypertrophic cardiomyopathy -- DCM dilated cardiomyopathy -- TNF tumor necrosis factor -- EF ejection fraction -- DEGs differentially expressed genes -- CNTs controls -- cTnI cardiac troponin I -- MAPK mitogen-activated protein kinase -- TTN Titin -- OBSCN obscurin; Heart failure -- RNA-Seq analysis -- Whole exome sequencing -- OAS1 mutation -- Phosphorylation dysregulation -- Immune signalling; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2022.11.029
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: Heart failure (HF) is a complex pathophysiological state characterized by inadequate delivery of blood and nutrients to the cardiac tissues. It is rarely curable and is commonly associated with a poor prognosis. In this study, we aimed to analyse exomic and RNA-Seq data from patients with HF to identify the key altered pathways in HF. Methods: Whole blood samples were collected from patients with HF and subjected to whole exome sequencing (WES) and RNA-Seq analysis. The gene expression and RNA-Seq data obtained were verified using gene chip analysis and RT-PCR. Results: Both exomic and RNA-Seq data confirmed the dysregulation of phosphorylation and immune signalling in patients with HF. Specifically, exomic analysis showed that TITIN, OBSCURIN, NOD2, CDH2, MAP3K5, and SLC17A4 mutations were associated with HF, and RNA-Seq revealed that S100A12, S100A8, S100A9, PFDN5, and TMCC2, were upregulated in patients with HF. Additionally, comparison between RNA-seq and WES data showed that OAS1 mutations are associated with HF. Conlcusion: Our findings indicated that patients with HF show an overall disruption of key phosphorylation and immune signalling pathways. Based on RNA-seq and WES, OAS1 mutations may be primarily responsible for these changes. Highlights: In this study, we analyzed the whole exome and RNA sequencing data of patients with (HF) in comparison to healthy individuals and the results indicated dysregulation of phosphorylation and immune signalling pathways in HF. In this study, we identified mutations in TITIN, OBSCURIN, NOD2, CDH2, MAP3K5, and SLC17A4 that were associated with HF. S100A12, S100A8, S100A9, PFDN5, and TMCC2, were found upregulated in patients with HF by RNA-Seq. OAS1 may be the key to be changed both by RNA-seq and WES.