title: Blood transcriptional signature of recombinant human erythropoietin administration and implications for antidoping strategies.
abstract: Recombinant human erythropoietin (rHuEPO) is frequently abused by athletes as a performance-enhancing drug, despite being prohibited by the World Anti-Doping Agency. Although the methods to detect blood doping, including rHuEPO injections, have improved in recent years, they remain imperfect. In a proof-of-principle study, we identified, replicated, and validated the whole blood transcriptional signature of rHuEPO in endurance-trained Caucasian males at sea level (n = 18) and Kenyan endurance runners at moderate altitude (n = 20), all of whom received rHuEPO injections for 4 wk. Transcriptional profiling shows that hundreds of transcripts were altered by rHuEPO in both cohorts. The main regulated expression pattern, observed in all participants, was characterized by a "rebound" effect with a profound upregulation during rHuEPO and a subsequent downregulation up to 4 wk postadministration. The functions of the identified genes were mainly related to the functional and structural properties of the red blood cell. Of the genes identified to be differentially expressed during and post-rHuEPO, we further confirmed a whole blood 34-transcript signature that can distinguish between samples collected pre-, during, and post-rHuEPO administration. By providing biomarkers that can reveal rHuEPO use, our findings represent an advance in the development of new methods for the detection of blood doping.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
authors.forename: Jérôme
authors.initials: J
authors.lastname: Durussel
authors.affiliation: Department of Medical Physiology, Addis Ababa University, Addis Ababa, Ethiopia;
authors.forename: Diresibachew W
authors.initials: DW
authors.lastname: Haile
authors.affiliation: Faculty of Sport and Exercise Sciences, University of Tartu, Tartu, Estonia;
authors.forename: Kerli
authors.initials: K
authors.lastname: Mooses
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom;
authors.forename: Evangelia
authors.initials: E
authors.lastname: Daskalaki
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
authors.forename: Wendy
authors.initials: W
authors.lastname: Beattie
authors.affiliation: Faculty of Sport and Exercise Sciences, University of Tartu, Tartu, Estonia;
authors.forename: Martin
authors.initials: M
authors.lastname: Mooses
authors.affiliation: Department of Medical Physiology, Addis Ababa University, Addis Ababa, Ethiopia;
authors.forename: Wondyefraw
authors.initials: W
authors.lastname: Mekonen
authors.affiliation: Department of Medical Physiology, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya; and.
authors.forename: Neford
authors.initials: N
authors.lastname: Ongaro
authors.affiliation: Department of Medical Physiology, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya; and.
authors.forename: Edwin
authors.initials: E
authors.lastname: Anjila
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
authors.forename: Rajan K
authors.initials: RK
authors.lastname: Patel
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
authors.forename: Neal
authors.initials: N
authors.lastname: Padmanabhan
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
authors.forename: Martin W
authors.initials: MW
authors.lastname: McBride
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;
authors.forename: John D
authors.initials: JD
authors.lastname: McClure
authors.affiliation: FIMS Reference Collaborating Centre of Sports Medicine for Anti-Doping Research, University of Brighton, Eastbourne, United Kingdom y.pitsiladis@brighton.ac.uk.
authors.forename: Yannis P
authors.initials: YP
authors.lastname: Pitsiladis
mesh_terms: D000328:Adult; D004300:Doping in Sports / Q000517:prevention & control*; D004921:Erythropoietin / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin
keywords: blood doping; erythropoiesis, mRNA