Doping by mutant athletes undetected

Jenny Jakobsson Schulze recently completed her thesis on the effect of genetic factors on the variation of masculine sex steroids concentration in urine and blood between individuals. She was one of the researchers involved in this study. “It has been known for a while that the level of testosterone in urine varies amongst the population, but we are the first to show that the differences can be related to genetic variations,” she explains.

Peeing under the limit
The study, conducted at the Karolinska Institute, Sweden, shows that 40 percent of the people who carry double copies of a particular gene variant do not reach the limit used to trace illicit testosterone preparations even though they have been administered a single dosage of the hormone.

The most common test for anabolic androgen steroids measures the levels of the testosterone hormone and epitestosterone in urine. This is because it is difficult to differentiate between natural and synthetic testosterone. As the epitestosterone level does not vary from person to person the quotient of the two steroids is used to determine if the body has been administered extra testosterone. The testosterone-epitestosterone quotient is normally circa 1,0. If it is higher than 4 the individual is suspected of doping and is subjected to further tests.
Jenny Jakobsson Schulzes’s study now shows that nearly half of those carrying two copies of the mutated gene would not be exposed in a regular doping test. The results also show that people with only one set of the gene measured levels just over the limit.

Common gene in Asia
The gene in question, mutated in some, plays an important role when testosterone is to be emitted through urine. It codes the enzyme that adds a molecule to the testosterone and makes it water soluble. The testosterone level in blood, however, remains the same, irrespective of gene mutation. Researchers still do not know if the mutated gene has any health consequences. “One hypothesis that we would like to investigate, is that people with the mutated gene variant are more strongly affected by anabolic androgen steroids since the testosterone seems to stay in the body for a longer period of time,” states Jenny Jakobsson Schulze.

The mutated variant of the gene exists in around ten percent of the Swedish population and in 70 percent of the population in Asian countries, including China, Japan, and Korea.
These people could thus take steroids without being found out by the conventional urine test. But there are other techniques that could expose the cheaters. The World Anti-Doping Agency (WADA) is therefore debating changing the doping tests. “Now that this gene variant is identified we may be able to reveal more cases of testosterone doping by carrying out further tests,” says Thomas Murray, Chairman of WADA’s ethical committee. He emphasizes, however, that the study only shows that testosterone emission is less effective in people carrying the mutated gene. How the break down of other synthetic steroids is affected remains unclear. “Further studies are needed to determine the importance of this discovery,” states Thomas Murray.

Gene test an alternative
Supplementing conventional tests with a gene analysis could be an alternative. The limit could then be lowered for individuals carrying the gene variant. “If the quotient is lowered from four to one there is as great a chance of catching the individuals with the mutated gene in the screening process carried out with others,” Jakobsson Schulze says.

False positive results
Jenny Jakobsson Schulz has also found other genes with a possible effect on doping tests, but none showed as clear an effect as the gene in question. One of the genes, however, could serve to explain some cases of false positive results as it affects the level of epitestosterone in urine. A lower than normal level of epitestosterone results in a higher quotient in doping tests. Such mistakes are cleared when other control tests are carried out, but it still means extra work and unnecessary worry for the person being tested.

Jakobsson Schulze now wants to proceed with her research. “This was a pilot study. We will proceed with a larger study including more people and higher dosages,” she explains.