Blood gene expression profiles of trained athletes in response to altitude exposure and differentiation from rHuEpo doping

The use of recombinant human erythropoietin (rHuEpo) is prohibited by the World Anti-Doping Agency (WADA). Using gene microarray technology, we have previously shown that blood gene expression profiles were significantly altered in response to rHuEpo administration both during- and for at least four weeks post administration. Confounders such as altitude exposure and training have the potential to compromise the molecular signature of rHuEpo doping. Purpose: To differentiate the gene expression profile due to strenuous training at altitude from rHuEpo doping. Method: Four (3 males and 1 female) well-trained athletes were exposed to altitude for periods ranging from 3-5 weeks. At altitude, subjects undertook strenuous training involving in two cases as much as 50 km each day for 18 days. One of the subjects had repeated exposure to altitude. Blood was obtained before, during and after altitude exposure. RNA from blood stabilized in Tempus RNA tubes was hybridized to HumanHT-12v4 Expression Illumina BeadChips and altitude-induced molecular responses were compared to the molecular signature of rHuEpo doping previously identified. Results: Preliminary data are encouraging and reveal significant overlap but also differentiation in responses to altitude and rHuEpo. Conclusion: These results provide further support for the use of blood gene biomarkers to improve the performance of current anti-doping methods such as the Athlete Biological Passport for rHuEpo detection.