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Genomic and RNA-Seq profiling of patients with HFrEF unraveled OAS1 mutation and aggressive expression

  • Author Footnotes
    1 These authors contributed equally to this work.
    Xin Li
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China

    Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Beijing 100853, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Yanying Shen
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Xiang Xu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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  • Ge Guo
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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  • Yibing Chen
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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  • Qingxia Wei
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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  • Hanlu Li
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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  • Kunlun He
    Correspondence
    Corresponding author at: Medical Big Data Research Center, Chinese PLA General Hospital, Beijing, China.
    Affiliations
    Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Beijing 100853, China

    Medical Big Data Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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  • Chunlei Liu
    Correspondence
    Corresponding author at: Transformation Medicine Centre, Chinese PLA General Hospital, Beijing, China.
    Affiliations
    Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China

    Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Beijing 100853, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:November 19, 2022DOI:https://doi.org/10.1016/j.ijcard.2022.11.029

      Highlights

      • Heart failure (HF) is a major public health problem worldwide; however, occurrence of HF in patients with underlying conditions has not been clearly unraveled.
      • In this study, we analyzed the whole exome and RNA sequencing data of patients with (HF) in comparison to healthy individuals to identify the pathways that are altered during occurrence of HF.
      • The results indicated dysregulation of phosphorylation and immune signalling pathways in HF, and 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. Our study revealed the key pathways and genes implicated in HF.
      • We believe that our study makes a significant contribution to the literature because the findings could identify overall disruption of key signalling pathways in patients with HF and suggested potential targets for clinical therapy.

      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.

      Abbreviations:

      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)

      Keywords

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