title: Circulating miR-148b-3p and miR-409-3p as biomarkers for heart failure in patients with mitral regurgitation.
abstract: BACKGROUND
  MicroRNAs (miRs) regulate gene expression in heart failure. Circulating miRs as biomarkers for heart failure in mitral regurgitation patients (MR) remain unexplored.
  
  
  METHODS
  This case-control study enrolled 32 MR patients with heart failure, 16 asymptomatic MR patients, and 12 control subjects without heart failure. We used next generation sequencing to study the gene expression profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in the left atria.
  
  
  RESULTS
  Next generation sequencing analysis and enrichment analysis showed that 25 miRs were differentially expressed in the sera of MR patients with heart failure compared to control subjects. The circulating miR-148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in the MR patients with heart failure compared to control subjects. However, only circulation miR-148b-3p was significantly down-regulated in the MR patients without heart failure compared to control subjects (p=0.009). The tissue miR-409-3p was significantly down-regulated in the MR patients with heart failure compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3 mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR patients with heart failure compared to normal controls (p=0.010). The tissue FRY (p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were significantly up-regulated in the MR patients with heart failure compared to normal controls.
  
  
  CONCLUSIONS
  Circulating miR-148b-3p might serve as biomarker for future development of heart failure and miR-409-3p might serve as biomarker for incident heart failure in MR patients.
authors: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan. Electronic address: chenmien@ms76.hinet.net.
authors: Mien-Cheng
authors: MC
authors: Chen
authors: Graduate Institute of Biomedical Informatics, Taipei Medical University, Taiwan.
authors: Tzu-Hao
authors: TH
authors: Chang
authors: Division of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan.
authors: Jen-Ping
authors: JP
authors: Chang
authors: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Taiwan.
authors: Hsien-Da
authors: HD
authors: Huang
authors: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan.
authors: Wan-Chun
authors: WC
authors: Ho
authors: Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors: Yu-Sheng
authors: YS
authors: Lin
authors: Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors: Kuo-Li
authors: KL
authors: Pan
authors: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan.
authors: Wen-Hao
authors: WH
authors: Liu
authors: Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors: Yao-Kuang
authors: YK
authors: Huang
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006333:Heart Failure / Q000209:etiology / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000150:complications / Q000235:genetics; D013624:Taiwan
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; C550570:MIRN148 microRNA, human; C572367:MIRN409 microRNA, human; D035683:MicroRNAs
keywords: Atrium; Genes; Heart failure; Mitral regurgitation