title: miRNAs and sports: tracking training status and potentially confounding diagnoses.
abstract: The dependency of miRNA abundance from physiological processes such as exercises remains partially understood. We set out to analyze the effect of physical exercises on miRNA profiles in blood and plasma of endurance and strength athletes in a systematic manner and correlated differentially abundant miRNAs in athletes to disease miRNAs biomarkers towards a better understanding of how physical exercise may confound disease diagnosis by miRNAs.
  
  
  
  We profiled blood and plasma of 29 athletes before and after exercise. With four samples analyzed for each individual we analyzed 116 full miRNomes. The study set-up enabled paired analyses of individuals. Affected miRNAs were investigated for known disease associations using network analysis.
  
  
  
  MiRNA patterns in blood and plasma of endurance and strength athletes vary significantly with differences in blood outreaching variations in plasma. We found only moderate differences between the miRNA levels before training and the RNA levels after training as compared to the more obvious variations found between strength athletes and endurance athletes. We observed significant variations in the abundance of miR-140-3p that is a known circulating disease markers (raw and adjusted p value of 5 × 10(-12) and 4 × 10(-7)). Similarly, the levels of miR-140-5p and miR-650, both of which have been reported as makers for a wide range of human pathologies significantly depend on the training mode. Among the most affected disease categories we found acute myocardial infarction. MiRNAs, which are up-regulated in endurance athletes inhibit VEGFA as shown by systems biology analysis of experimentally validated target genes.
  
  
  
  We provide evidence that the mode and the extent of training are important confounding factors for a miRNA based disease diagnosis.
authors.affiliation: Institute of Sports and Preventive Medicine, Saarland University, Saarbrücken, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Hecksteden
authors.affiliation: Department of Human Genetics, Saarland University, Saarbrücken, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.affiliation: Chair for Clinical Bioinformatics, Medical Department, Saarland University, Building E2.1, 66125, Saarbrücken, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Department of Human Genetics, Saarland University, Saarbrücken, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rheinheimer
authors.affiliation: Department of Theory and Practice of Sports, Johannes Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Pfeiffer
authors.affiliation: Faculty of Sport Science, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ferrauti
authors.affiliation: Faculty of Sport Science, Ruhr-University Bochum, Bochum, Germany.|School of Human Movement Studies, The University of Queensland, St Lucia, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kellmann
authors.affiliation: Internal Medicine, Heidelberg University, Heidelberg, Germany.
authors.forename: Farbod
authors.initials: F
authors.lastname: Sedaghat-Hamedani
authors.affiliation: Internal Medicine, Heidelberg University, Heidelberg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meder
authors.affiliation: Department of Human Genetics, Saarland University, Saarbrücken, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.affiliation: Institute of Sports and Preventive Medicine, Saarland University, Saarbrücken, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Chair for Clinical Bioinformatics, Medical Department, Saarland University, Building E2.1, 66125, Saarbrücken, Germany. andreas.keller@ccb.uni-saarland.de.
authors.forename: Andreas
authors.identifier: 0000-0002-5361-0895
authors.initials: A
authors.lastname: Keller
mesh_terms: D016000:Cluster Analysis; D015986:Confounding Factors, Epidemiologic; D015444:Exercise / Q000502:physiology*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D025341:Principal Component Analysis; D055070:Resistance Training; D013177:Sports
chemical_list: D035683:MicroRNAs