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'Right' gene lets you inject testosterone without getting caught by doping test

Athletes with a defective gene in their DNA can inject testosterone without testing positive in the usual doping tests, write researchers at the Karolinska University in the Journal of Clinical Endocrinology and Metabolism.

The gene that protects doping athletes from doping hunters is a variant of UGT2B17. This is the gene that is responsible for the production of the enzyme uridinediphospho glucuronosyl transferase 2B17 in cells. UGTs attach sugars to androgens so that the body can eliminate them. Each UGT has a preference for a specific set of androgens. UGT2B15 for example goes for the DHT metabolite androstane-3alpha,17beta-diol. UGT2B17, the gene/enzyme that the Swedes studied, attaches sugars to epitestosterone. [Structure below]

Epitestosterone is released when the cells in the body that produce hormones also release testosterone. This means that there is a constant ratio in the body between the amount of testosterone and epitestosterone. If you inject testosterone, the proportions change. It's this that alerts doping hunters to the use of exogenous testosterone. If the T/E ratio [the scientific name for the relationship between the amount of testosterone and the amount of epitestosterone] rises above four, doping hunters declare an athlete positive.

But, the Swedes want to know, what happens if the gene for UGT2B17 doesn't work properly? That means you always have relatively high levels of epitestosterone in your body, and you might be able to use more testosterone without the test picking up on this.

Your DNA has two examples of each your genes, so also of UGT2B17. In the graphs below, ins/ins stands for test subjects with two correctly functioning examples; del/del stands for test subjects in which both examples are defective; and del/ins for test subjects with one defective and one correct version of the gene.

The researchers gave their test subjects a single injection of 500 mg of Testoviron active compound: testosterone enanthate. The graph below shows what happened to their T/E ratios over a period of two weeks.

'Right' gene lets you inject testosterone without getting caught by doping test

When the researchers looked at whether their test subjects scored positive for a doping test, they got the graph below. As you can see, forty percent of the test subjects with two defective versions of UGT2B17 never get anywhere near the T/E ratio of four.

'Right' gene lets you inject testosterone without getting caught by doping test

The genetic variants that the Swedes looked at are not rare. Almost ten percent of Swedes have the del/del variant. In Asian countries the percentage is even higher: in Korea, for example, two-thirds of the population has this variant. So Asian chemical athletes that use testosterone slip more easily through the net than their European counterparts.

J Clin Endocrinol Metab. 2008 Jul;93(7):2500-6.