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RNA biomarkers in antidoping.

Olivier Salamin1, Tiia Kuuranne1, Nicolas Leuenberger1

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New RNA biomarkers offer a promising advancement for the Athlete Biological Passport (ABP) in sports doping detection. Blood transcriptomics, using messenger RNAs (mRNAs) and microRNAs (miRNAs), enhances sensitivity beyond current methods.

Keywords:
Athlete biological passportBiomarkersDopingmRNAmiRNA

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Area of Science:

  • Sports Science
  • Biomarker Discovery
  • Molecular Biology

Background:

  • Traditional doping detection relies on exogenous substance identification, which is limited for pseudo-endogenous compounds like testosterone and recombinant human erythropoietin (rhEPO).
  • The Athlete Biological Passport (ABP) was developed for longitudinal monitoring of biological responses, but faces limitations in biomarker repertoire and susceptibility to sophisticated doping strategies.

Purpose of the Study:

  • To explore RNA-based biomarkers, specifically messenger RNAs (mRNAs) and microRNAs (miRNAs), as complementary tools to enhance the Athlete Biological Passport (ABP).
  • To assess the potential of blood transcriptomics and dried blood spots (DBS) for improving doping detection sensitivity and feasibility.

Main Methods:

  • Analysis of blood transcriptomics, focusing on gene expression changes indicative of erythropoietic stimulation and blood manipulation (e.g., ALAS2, CA1).
  • Investigation of dried blood spots (DBS) as a sample matrix for RNA biomarker analysis, evaluating its impact on collection, storage, and transport.
  • Review of potential applications and necessary validation steps for integrating RNA biomarkers into anti-doping frameworks.

Main Results:

  • Blood transcriptomics provides sensitive indicators of erythropoietic stimulation and blood manipulation in response to rhEPO and transfusion.
  • Dried blood spots (DBS) offer a feasible method for RNA analysis, preserving RNA integrity while simplifying sample handling.
  • RNA biomarkers show translational potential in equine anti-doping and clinical applications for anemia treatment.

Conclusions:

  • RNA profiling, including mRNAs and miRNAs, represents a next-generation biomarker strategy to expand the ABP framework.
  • Integration of RNA biomarkers can significantly improve the sensitivity and effectiveness of global anti-doping programs.
  • Further validation, harmonization, and regulatory development are crucial for the successful implementation of RNA biomarkers in anti-doping.