Modification of gene expression: Help to detect doping with erythropoiesis‐stimulating agents

Abstract

Enhanced oxygen delivery to tissues has been shown to improve endurance performance [1]. This has led to widespread abuse of erythropoiesis-stimulating agents (ESA) in elite sport. It is conceivable that athletes have even learned how to continue illicit ESA doping [2]. This possibility has fuelled the search for novel methods to detect and deter ESA abuse using indirect markers. It is now widely accepted that drugs influence gene expression [3,4]. In this study, we envisage its use as a means to detect ESA doping. We obtained a global view of the transcriptome of total blood cells both before and after treatment with darbepoetin alpha using the serial analysis of gene expression (SAGE) method. In silico analysis identified 95 genes whose differential expression was subsequently tested by quantitative real-time polymerase chain reaction (PCR) in two athletes. The athletes were treated first with high doses of recombinant human erythropoietin (rHuEpo) to increase their hemoglobin concentration and then with microdoses to maintain the high concentration of hemoglobin. Significance analysis of microarrays (SAM) at a delta ratio greater than 1.5 indicated that 33 genes could be significant markers of ESA administration. Interestingly, when high and microdoses were taken into account together, five genes could still be considered as significant markers.