title: Utility of Select Plasma MicroRNA for Disease and Cardiovascular Risk Assessment in Patients with Rheumatoid Arthritis.
abstract: OBJECTIVE
  MicroRNA (miRNA) are small noncoding RNA that posttranscriptionally regulate gene expression and serve as potential mediators and markers of disease. Recently, plasma miR-24-3p and miR-125a-5p concentrations were shown to be elevated in rheumatoid arthritis (RA) and useful for RA diagnosis. We assessed the utility of 7 candidate plasma miRNA, selected for biological relevance, for RA diagnosis and use as markers of disease activity and subclinical atherosclerosis in RA.
  
  
  METHODS
  The cross-sectional study included 168 patients with RA and 91 control subjects of similar age, race, and sex. Plasma concentrations of miR-15a-5p, miR-24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were measured by quantitative PCR. Utility of plasma miRNA concentrations for RA diagnosis was assessed by area under the receiver-operating characteristic curve (AUROC). Associations between plasma miRNA concentrations and RA disease activity and coronary artery calcium score were assessed by Spearman correlations.
  
  
  RESULTS
  Plasma concentrations of miR-15a-5p, miR-24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were significantly increased in patients with RA. The highest AUROC for diagnosis of RA (AUROC = 0.725) was found in miR-24-3p, including among rheumatoid factor-negative patients (AUROC = 0.772). Among all patients with RA, the combination of miR-24-3p, miR-26a-5p, and miR-125a-5p improved the model modestly (AUROC = 0.747). One miRNA, miR-155-5p, was weakly inversely associated with swollen joint count (p = 0.024), but no other miRNA were associated with disease activity or coronary artery calcium score.
  
  
  CONCLUSIONS
  The combination of miR-24-3p, miR-26a-5p, and miR-125a-5p had the strongest diagnostic accuracy for RA. Candidate miRNA had little or no association with RA disease activity or subclinical atherosclerosis.
authors.affiliation: Department of Medicine and Division of Rheumatology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Ormseth
authors.affiliation: Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Solus
authors.affiliation: Department of Medicine and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kasey C
authors.initials: KC
authors.lastname: Vickers
authors.affiliation: Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Oeser
authors.affiliation: Department of Medicine and Division of Cardiology, University of Alberta, Edmonton, Canada.
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.affiliation: Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: ATHEROSCLEROSIS; CARDIOVASCULAR RISK; DIAGNOSIS; DISEASE ACTIVITY; MICRORNA; RHEUMATOID ARTHRITIS