The blood transcriptional signature of recombinant human erythropoietin administration and implications for anti-doping strategies

Jérôme Durussel, Diresibachew W. Haile, Kerli Mooses, Evangelia Daskalaki, Wendy Beattie, Martin Mooses, Wondyefraw Mekonen, Neford Ongaro, Edwin Anjila, Rajan K. Patel, Neal Padmanabhan, Martin W. McBride, John D. McClure, Yannis P. Pitsiladis

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: 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. Methods: 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 four weeks. Results: Transcriptional profiling shows that hundreds of transcripts were altered by rHuEPO in both cohorts. The main regulated expression pattern, observed in all participants, was characterised by a "rebound" effect with a profound up-regulation during rHuEPO and a subsequent down-regulation up to four weeks post administration. 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. Conclusion: By providing biomarkers that can reveal rHuEPO use, our findings represent a substantial advance in the development of new enhanced and robust methods for the detection of blood doping.
LanguageEnglish
Pages202-209
Number of pages8
JournalPhysiological genomics
Volume48
Issue number3
DOIs
Publication statusPublished - 1 Mar 2016

Fingerprint

Erythropoietin
Doping in Sports
Performance-Enhancing Substances
Injections
Oceans and Seas
Athletes
Genes
Up-Regulation
Down-Regulation
Erythrocytes
Biomarkers

Keywords

  • anti-doping strategies
  • recombinant human erythropoietin
  • blood doping

Cite this

Durussel, Jérôme ; Haile, Diresibachew W. ; Mooses, Kerli ; Daskalaki, Evangelia ; Beattie, Wendy ; Mooses, Martin ; Mekonen, Wondyefraw ; Ongaro, Neford ; Anjila, Edwin ; Patel, Rajan K. ; Padmanabhan, Neal ; McBride, Martin W. ; McClure, John D. ; Pitsiladis, Yannis P. / The blood transcriptional signature of recombinant human erythropoietin administration and implications for anti-doping strategies. In: Physiological genomics. 2016 ; Vol. 48, No. 3. pp. 202-209.
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Durussel, J, Haile, DW, Mooses, K, Daskalaki, E, Beattie, W, Mooses, M, Mekonen, W, Ongaro, N, Anjila, E, Patel, RK, Padmanabhan, N, McBride, MW, McClure, JD & Pitsiladis, YP 2016, 'The blood transcriptional signature of recombinant human erythropoietin administration and implications for anti-doping strategies' Physiological genomics, vol. 48, no. 3, pp. 202-209. https://doi.org/10.1152/physiolgenomics.00108.2015

The blood transcriptional signature of recombinant human erythropoietin administration and implications for anti-doping strategies. / Durussel, Jérôme; Haile, Diresibachew W.; Mooses, Kerli; Daskalaki, Evangelia; Beattie, Wendy; Mooses, Martin; Mekonen, Wondyefraw; Ongaro, Neford; Anjila, Edwin; Patel, Rajan K.; Padmanabhan, Neal; McBride, Martin W.; McClure, John D.; Pitsiladis, Yannis P.

In: Physiological genomics, Vol. 48, No. 3, 01.03.2016, p. 202-209.

Research output: Contribution to journalArticle

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T1 - The blood transcriptional signature of recombinant human erythropoietin administration and implications for anti-doping strategies

AU - Durussel, Jérôme

AU - Haile, Diresibachew W.

AU - Mooses, Kerli

AU - Daskalaki, Evangelia

AU - Beattie, Wendy

AU - Mooses, Martin

AU - Mekonen, Wondyefraw

AU - Ongaro, Neford

AU - Anjila, Edwin

AU - Patel, Rajan K.

AU - Padmanabhan, Neal

AU - McBride, Martin W.

AU - McClure, John D.

AU - Pitsiladis, Yannis P.

N1 - Copyright © 2015, Physiological Genomics.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background: 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. Methods: 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 four weeks. Results: Transcriptional profiling shows that hundreds of transcripts were altered by rHuEPO in both cohorts. The main regulated expression pattern, observed in all participants, was characterised by a "rebound" effect with a profound up-regulation during rHuEPO and a subsequent down-regulation up to four weeks post administration. 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. Conclusion: By providing biomarkers that can reveal rHuEPO use, our findings represent a substantial advance in the development of new enhanced and robust methods for the detection of blood doping.

AB - Background: 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. Methods: 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 four weeks. Results: Transcriptional profiling shows that hundreds of transcripts were altered by rHuEPO in both cohorts. The main regulated expression pattern, observed in all participants, was characterised by a "rebound" effect with a profound up-regulation during rHuEPO and a subsequent down-regulation up to four weeks post administration. 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. Conclusion: By providing biomarkers that can reveal rHuEPO use, our findings represent a substantial advance in the development of new enhanced and robust methods for the detection of blood doping.

KW - anti-doping strategies

KW - recombinant human erythropoietin

KW - blood doping

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DO - 10.1152/physiolgenomics.00108.2015

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JO - Physiological genomics

T2 - Physiological genomics

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SN - 1094-8341

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