Evaluating Transcriptomic Biomarkers for rHuEPO Detection: Assessing the Impact of Exercise and Altitude Exposure

Recombinant human erythropoietin (rHuEPO) is often misused in endurance sports due to its potent erythropoietic effects. While transcriptomic biomarkers hold promise for detecting rHuEPO use beyond conventional testing windows, many proposed gene markers may also respond to physiological stimuli such as exercise or altitude. This study compared 153 previously reported rHuEPO-responsive genes in whole blood with transcripts identified during exercise (GEPREP database) and high-altitude exposure (four independent studies). For the exercise dataset, gene-level statistical outputs were obtained directly from the GEPREP database, while biological relevance was calculated using Cohen's d. Analyses of altitude and rHuEPO datasets followed the original statistical procedures described in each study. Among the 153 rHuEPO-responsive genes, 94 overlapped with altitude and 34 with exercise. However, 50 genes remained unaffected by either exercise or altitude stimuli. Enriched in post-translational regulation and intracellular transport pathways, these genes represent promising candidate transcriptomic markers of rHuEPO administration. This work provides a refined gene panel that reduces the likelihood of false positives and requires further experimental validation before integration into RNA-based detection tests.