Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration

Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration / Guan Wang, Jérôme Durussel, Jonathan Shurlock, Martin Mooses, Noriyuki Fuku, Georgie Bruinvels, Charles Pedlar, Richard Burden, Andrew Murray, Brendan Yee, Anne Keenan, John D. McClure, Pierre-Edouard Sottas, Yannis P. Pitsiladis. - (BMC Genomics 18 (2017) Supplement 8 (17 November); p. 67-113)

  • PMID: 29143667
  • PMCID: PMC5688496
  • DOI: 10.1186/s12864-017-4191-7


Background: Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo.

Methods: Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo.

Results: ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%).

Conclusions: Current results provide further evidence that transcriptional biomarkers can strengthen the ABP approach by significantly prolonging the detection window and improving the sensitivity and specificity of blood doping detection. Further studies are required to confirm, and if necessary, integrate the confounding effects of altitude training on blood doping.

Original document


Research / Study
14 November 2017
Bruinvels, Georgie
Burden, Richard
Durussel, Jérôme
Fuku, Noriyuki
Keenan, Anne
McClure, John D.
Mooses, Martin
Murray, Andrew
Pedlar, Charles
Pitsiladis, Yannis P.
Shurlock, Jonathan
Sottas, Pierre-Edouard
Wang, Guan
Yee, Brendan
United Kingdom
United States of America
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Brighton and Sussex Medical School (BSMS)
Juntendō Daigaku - Juntendo University
St Mary's University, Twickenham
Tartu Ülikool - University of Tartu (UT)
Università degli Studi di Roma "Foro italico" - Foro Italico University of Rome
University of Brighton
University of Edinburgh
University of Glasgow
Analytical aspects
Blood testing method
Testing method development
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S2. Peptide Hormones, Growth Factors
Erythropoietin (EPO)
Athlete Biological Passport (ABP)
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Scientific article
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Pdf file
Date generated
1 July 2021
Date of last modification
15 July 2021
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