Thursday, April 3, 2008

Genotype Variations in Enzyme UGT2B17: Implications

Dr. Jenny Jakobsson Schultz et.al, of the Karolinska Institute in Sweden, have published a study examining inherited variations of enzyme UGT2B17 and their effect on testosterone/epitestosterone ratio testing. Variations in UGT2B17 genotype may cause a false positive in the absence of doping or a false negative even after exogenous testosterone use.

Well, at least someone has found that individual differences in genotype does cause different testosterone/epitestosterone ratio results. WADA would have never conceded this: the golden standard of 4:1 is written in stone and "bullet proof." Yes. WADA is stubborn as an ox with these standards of what constitutes a doping violation and are very resistant to change. Even though most peer reviewed papers that deal with testosterone doping warn of subjects who have been found with natural testosterone/epitestosterone levels greater than 4:1.

One day scientific papers may warn of people who have one testosterone metabolite(s) above a 3 delta per mil threshold on an IRMS test is due to variations in genotype. They may warn of people who have variations in genotype expression of hepatic enzymes, or in first, second, or third messengers, or in G-proteins. WADA will have to alter their testing methods to accommodate this new information.

WADA Remains Resistant to Change.

WADA refuses to worry about trivial genetic factors. WADA is loath to do longitudinal tests of athletes. WADA might find a variable that might refute their laboratory findings or challenge their presumption of laboratory perfection. WADA would never invest time and money doing pedigree studies to determine if a single metabolite above threshold for exogenous testosterone is a trait common in a family, or among a group of people found in a geographical region. But idiosyncratic individual differences in medicine have been documented in many pedigree studies. For example, hematocrit levels above 50% have been found in fathers and sons of elite cyclists. These hematocirt levels are inherited tendencies, not based on EPO doping. The same is true for testosterone/epitestosterone ratio(s) and may be true for Carbon Isotope metabolite delta/delta scores.

No matter. WADA world can't even agree among the laboratories as to what criteria constitutes a positive IRMS result. The WADA Technical Documents are vague. Testosterone metabolites measured are selected at random. Uncertainty in measurement(s) are ignored. Laboratory personnel are unqualified in testing sequences, inexperienced, prone to make errors. But WADA will never invest the money needed to correct these problems. Why? Because WADA would rather budget to pay for prosecutions against athletes who appeal their bad lab results. WADA would rather defend idiots like Dick Pound from lawsuits. WADA would rather waste time with nonsense than to invest in hard science.

WADA abandoned the UCI biological passport system. Astana has more commitment and money invested in the UCI biological passport than WADA. Yet WADA maintains a myth of total commitment to anti-doping in sport.

Conclusion: The IRMS is an instrument that requires very precise controls of operation. The results of an IRMS is only as good as the laboratory performing the tests. Inexperienced laboratory personnel who cannot follow sequential steps in testing cannot be expected to arrive at the correct results. A valid IRMS is also only as good as the science behind the tests. A valid IRMS is only as good as the criteria required in WADA technical documents, by international standards, and by standardized criteria as to what constitutes a positive result. WADA has failed in all these areas.

One hundred years from now will the scientists of the future shake their heads in amazement at our ignorance. Will they abhor the stupidity and mistakes of the anti-doping crusade? Will they be forced to restore the honor to "fallen" athletes?

An appalling prospect, indeed.

1 comment:

ZENmud productions said...

hi Jon,

We could be working at WADA together, soon enough... or if WADAwatch becomes an NGO....?

Want to change careers?

DrewZEN