Sports doping test confounded by common genetic variation

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Washington, Mar 23 : A new study has found that tests for testosterone doping used in professional and amateur sports may normally be confounded by a common genetic variation.

Headed by Jenny J. Schulze, Ph.D, of the Karolinska University Hospital in Stockholm, the study also indicated that unless this variation is accounted for, current testing methods could implicate innocent athletes and allow cheaters to go undetected.

"Genetic factors may play an important role in the accuracy and sensitivity of testosterone doping tests. This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society," said Schulze.

Currently, the first-line defence for detecting testosterone abuse in sports is by measuring the ratio of two chemicals in a spot urine test: testosterone glucuronide (TG) and epitestosterone glucuronide (EG). TG is a by-product of testosterone in the body; it increases as the amount of testosterone increases. EG is not linked to testosterone metabolism, and serves as a reference point in testing.

According to the International Olympic Committee, in doping tests, any ratio above four should be considered suspicious and lead to further testing.

However, TG production from testosterone is mainly controlled by an enzyme (UGT2B17), produced by a specific gene. Common variations to this gene may give rise to wildly different testing results, even when the same dose of testosterone has been taken.

In the study, 145 men were screened for the insertion (ins) or deletion (del) of this gene. Among the participants, 15 percent had no copies of the gene (del/del), 52 percent had one copy (ins/del), and 33 percent carried two copies (ins/ins). From this group, 55 men (17 del/del, 24 ins/del, and 14 ins/ins) were selected to receive a single 360 mg dose of testosterone. Later, the men were routinely tested over a 15-day period for the symptoms of doping.

A full 40 percent of the del/del subjects never reached 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 360 mg dose of testosterone," said Dr. Schulze.

Similarly, 14 percent of the ins/ins subjects were naturally over the detection threshold even though they did not receive a testosterone injection. Based on an earlier study, it has been estimated that this would give a false-positive rate of 9 percent in a random population 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," said Dr. Schulze.

Ideally, the researchers suggest that, depending on the athlete's genotype, there should be different cut-off levels for doping tests.

The researchers said that although this variant can appear in any population, it is considerably more common in East Asians (approximately 65 percent) than in Swedish Caucasians (10 percent).

The study will be published in the Journal of Clinical Endocrinology and Metabolism (JCEM).

ANI

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