Blood transcriptional signature of recombinant human erythropoietin administration and implications for antidoping strategies

Durussel, J. et al. (2016) Blood transcriptional signature of recombinant human erythropoietin administration and implications for antidoping strategies. Physiological Genomics, 48(3), pp. 202-209. (doi: 10.1152/physiolgenomics.00108.2015) (PMID:26757800)

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.

• Item Type: Articles
• Additional Information: M. Mooses was supported by national scholarship program Kristjan Jaak, which is funded and managed by the Archimedes Foundation in collaboration with the Ministry of Education and Research. Both K. Mooses and M. Mooses were supported by European Social Fund’s Doctoral Studies and Internationalisation Programme DoRa, which is carried out by Foundation Archimedes. The research was funded by grant from WADA (08C19YP).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Patel, Dr Rajan and Mooses, Mr Martin and McBride, Dr Martin and Beattie, Mrs Wendy and Mooses, Ms Kerli and Durussel, Mr Jerome and Pitsiladis, Dr Yannis and Padmanabhan, Dr Neal and McClure, Dr John
• Authors: Durussel, J., Haile, D., Mooses, K., Daskalaki, E., Beattie, W., Mooses, M., Mekonen, W., Ongaro, N., Anjila, E., Patel, R., Padmanabhan, N., McBride, M., McClure, J., and Pitsiladis, Y.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Physiological Genomics
• Publisher: American Physiological Society
• ISSN: 1094-8341
• ISSN (Online): 1531-2267