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Headlines Published on 23 April 2008

HEALTH
Title The role of genes in doping tests

Sport is all about fair play. But for some athletes it is more about winning at all costs, even if it means using prohibited substances to improve their sporting performance. For many of these athletes, anabolic steroids, a class of steroid hormones related to the hormone testosterone, are the drug of choice. However, tests for testosterone doping may sometimes be inaccurate on account of genetic variations, a new study headed by the Karolinska University Hospital in Sweden has revealed.

Doping has reached new heights in the world of sport © Shutterstock
Doping has reached new heights in the world of sport
© Shutterstock

The World Anti-Doping Agency (WADA) standardises the rules and regulations governing anti-doping in professional and amateur sports internationally. The researchers of this study, however, point out that unless genetic variation is accounted for, the testing methods that are currently used could point the finger at the wrong people.

'Genetic factors may play an important role in the accuracy and sensitivity of testosterone doping tests,' explains Dr Jenny J. Schulze of the Karolinska University Hospital in Sweden and lead author of the study. 'This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society.'

In spot urine tests, the ratio of two chemicals testosterone glucuronide (TG) and epitestosterone glucuronide (EG) is measured. TG is a byproduct of testosterone in the body and boosts the hormone level, while EG serves as a reference point in testing but is not linked to testosterone metabolism. Based on International Olympic Committee standards, a ratio above four is regarded as suspicious.

A specific gene in the body is responsible for producing the enzyme UGT2B17, which largely controls the production of TG from testosterone. According to the researchers, common variations to this gene could trigger varying test results. This is true even if the same dose of testosterone has been administered.

The researchers screened 145 men for the insertion or deletion of this gene. A breakdown of the sample shows that 52% of the participants had one copy (insertion/deletion) of the gene, 33% had two copies (insertion/insertion), while 15% had no copies (deletion/deletion).

A single dose of 360 milligrammes of testosterone was given to 55 men (17 deletion/deletion; 24 insertion/deletion; and 14 insertion/insertion). The results show that 40% of the deletion/deletion participants did not reach the detection threshold in a standard doping test.

'Nearly half of the individuals in our study who carried this genetic variation would go undetected in a regular doping test after a single 360mg dose of testosterone,' says Dr Schulze.

It should be noted that 14% of the insertion/insertion subjects surpassed the detection threshold despite not being injected with the testosterone. According to the researchers, this would give a false-positive rate of 9% in a random sample of young men. 'False positive results are not only of concern for the legal rights of the sportsman, they also yield extra workload for the doping laboratories, believes Dr Schulze.

If possible, the genotype of each athlete should be taken into consideration when determining the cut-off levels for doping tests, the researchers argue. Latest data show this variant is considerably more common in East Asians (about 65%) compared with Swedish Caucasians (10%), they add.

The paper 'Doping Test Results Dependent on Genotype of UGT2B17, the Major Enzyme for Testosterone Glucuronidation' will be published in the June issue of the Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of The Endocrine Society.









More information:

  • The Endocrine Society
  • The Journal of Clinical Endocrinology & Metabolism
  • EU and Sport







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