An integrative ‘Omics’ solution to the detection of recombinant human erythropoietin and blood doping

Abstract

Administration of recombinant human erythropoietin (rHumanEPO) improves sporting performance and hence is frequently subject to abuse by athletes, although rHumanEPO is prohibited by the WADA. Approaches to detect rHumanEPO doping have improved significantly in recent years but remain imperfect. A new transcriptomic-based longitudinal screening approach is being developed that has the potential to improve the analytical performance of current detection methods. In particular, studies are being funded by WADA to identify a 'molecular signature' of rHumanEPO doping and preliminary results are promising. In the first systematic study to be conducted, the expression of hundreds of genes were found to be altered by rHumanEPO with numerous gene transcripts being differentially expressed after the first injection and further transcripts profoundly upregulated during and subsequently downregulated up to 4 weeks postadministration of the drug; with the same transcriptomic pattern observed in all participants. The identification of a blood 'molecular signature' of rHumanEPO administration is the strongest evidence to date that gene biomarkers have the potential to substantially improve the analytical performance of current antidoping methods such as the Athlete Biological Passport for rHumanEPO detection. Given the early promise of transcriptomics, research using an 'omics'-based approach involving genomics, transcriptomics, proteomics and metabolomics should be intensified in order to achieve improved detection of rHumanEPO and other doping substances and methods difficult to detect such a recombinant human growth hormone and blood transfusions.

Challenges and threats to implementing the fight against doping in sport

“…For example, the molecular signature of rHuEPO doping has been discovered recently. This success provides the strongest evidence until now that state-of-the-art ‘omics’ technologies have the potential to significantly strengthen the current ABP approach and contribute to other traditional antidoping tests 12. A next generation ABP that also combines blood and steroid profiles is expected to be a substantial improvement.…”

Metabolômica: Definições, Estado-Da-Arte E Aplicações Representativas

“…Para investigar a origem da biossíntese nestas condições a quantificação de acetil-CoA foi realizada através da análise por MS e traçadores marcados com C-13, em células cancerígenas (HeLA e A549) e saudáveis (MDA MD468 114 A metabolômica se apresenta como uma ferramenta inovadora para elucidar os complexos mecanismos associados à prática de exercícios físicos, relevantes para a saúde humana. Por muito tempo, essa abordagem foi especialmente aplicada à análise de controle do abuso de drogas proibidas no esporte, sendo muito utilizada para testes anti-doping em humanos, [115][116][117][118] nas quais amostras de urina e plasma de atletas são analisadas; entretanto, um biofluido alternativo, o suor, tem sido proposto como um novo tipo de amostra para realização desses testes. 119 Progressos nas técnicas de detecção e métodos de análise têm sido apresentados com o objetivo de se buscar biomarcadores de doping.…”

Blood doping: potential of blood and urine sampling to detect autologous transfusion

“…There is also loss of carbohydrates, proteins and membrane lipids. Alongside ‘omics’, methods are being proposed for the detection of recombinant EPO47 or other doping substances; proteomic methods—among others— have shown the changes in the proteome of erythrocyte membranes over time, such as translocations, loss of protein or storage 48–50…”