title: Circulating microRNA Profiling Needs Further Refinement Before Clinical Use in Patients With Aortic Stenosis.
abstract: BACKGROUND
  Aortic stenosis (AS) is a progressive condition leading to heart failure and death without treatment. No medical therapy currently exists for AS, and a major management challenge is deciding on the correct timing of aortic valve replacement. MicroRNAs (miRNAs) are short noncoding RNAs that are stable in the circulation. We wished to use miRNAs as biomarkers of disease in AS.
  
  
  RESULTS
  We performed microarray-based whole miRNome profiling of 24 participants with AS and 27 control participants. After adjustment for age and multiple testing, we identified 4 miRNAs significantly different between groups. These findings were then examined using quantitative polymerase chain reaction in a larger validation cohort of 101 controls and 94 participants with AS, stratified in a prespecified analysis by presence of coexisting coronary artery disease (CAD). We obtained mixed results for miR-22-3p, miR-24-3p, miR-382-5p, and miR-451a in the validation cohort, with differing associations according to CAD status. miR-21-5p was increased in AS patients without CAD, but there was no difference between groups with CAD.
  
  
  CONCLUSIONS
  Despite holding great promise, circulating miRNA profiling requires further refinement before translation into clinical use as a biomarker in aortic stenosis.
authors: Department of Cardiology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom (S.C.) Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (S.C., M.A.W.).
authors: Sean
authors: S
authors: Coffey
authors: Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (S.C., M.A.W.).
authors: Michael J A
authors: MJ
authors: Williams
authors: Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (V.P., G.T.J.).
authors: L Vicky
authors: LV
authors: Phillips
authors: Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (V.P., G.T.J.).
authors: Gregory T
authors: GT
authors: Jones
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D056726:Genetic Association Studies; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs
keywords: aortic valve stenosis; biomarker; microRNA