Impact of UGT2B17 gene deletion on the steroid profile of an athlete

Abstract

The measurement of the testosterone to epitestosterone ratio (T/E ratio) in urine is often used as a marker for testosterone administration in the doping control field. This study examines the frequencies of the different expression forms of the UGT2B17 gene, and assesses their effects on this marker in volunteer subjects. The sample for this descriptive study was composed of male and female athletes aged between 16 and 55 years old who practiced different sports disciplines. All participants underwent a sports‐medical physical examination, and subsequently provided 10 urine samples consecutively over a period of 48 h. The dependent variable examined was T/E and the main independent variable was the UGT2B17 gene polymorphism. During 1 year, 1410 urine samples were obtained from 141 athletes. The frequencies of the three genotypes were as follows: wt homozygotes (ins/ins) 48.2% (n = 68), mutant homozygotes (del/del) 12.1% (n = 17), and heterozygotes (ins/del) 39.7% (n = 56). Genotype distributions varied significantly (P < 0.001) according to ethnicity, 80% of Asian subjects being homozygous for the gene deletion (del/del) compared to 6.9% of Caucasian subjects. A multivariate analysis adjusted for genotype, age, sex, and sports discipline revealed that athletes with the del/del polymorphism showed a significantly lower mean T/E than heterozygotes (ins/del). In contrast, homozygous athletes for the gene insertion (ins/ins) showed higher mean T/E ratios than heterozygotes (ins/del). UGT2B17 gene deletion has a strong influence on the T/E ratio in urine, which is the most efficient indicator of testosterone prohormone misuse. Others factors studied seem not to have such an impact. The genotyping of UGT2B17 is an important source of information for understanding steroid profiling in the doping control field; therefore it is suggested that it be included in the Athletes Biological Passport.

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

“…UGT2B17 polymorphisms also pose a significant challenge in detection of testosterone doping by athletes, where metabolite ratios are used to create individual biological passports. 26,27 Therefore, to test if the testosterone metabolite ratios are doseindependent, we quantified complete testosterone metabolite panel after treating with two oral doses (200 and 800 mg).…”

Sensitivity of doping biomarkers after administration of a single dose testosterone gel

“…7,8 We have previously described the concordance between the UGT2B17 deletion polymorphism and the urinary excretion of testosterone. 9 Individuals devoid of the UGT2B17 gene display lower T/E ratios than those with 1 or 2 insertion polymorphism, 8,10 and after administration of testosterone these individuals rarely reach a T/E ratio above 4. [11][12][13] It is known that transdermal administration of T gel causes an increase in serum T and dihydrotestosterone (DHT), markers that have been suggested for longitudinal monitoring in a blood steroid profile.…”

“…We have previously described the concordance between the UGT2B17 deletion polymorphism and the urinary excretion of testosterone . Individuals devoid of the UGT2B17 gene display lower T/E ratios than those with 1 or 2 insertion polymorphism, and after administration of testosterone these individuals rarely reach a T/E ratio above 4 …”

Annual banned‐substance review: analytical approaches in human sports drug testing

“…Here, however, the authors concluded that if the genotype ( del / del ) would have been a known parameter and factored in, the monitored profile would also have been considered suspicious. Due to its critical role, the addition of the athletes’ UGT2B17 genotype has been suggested to be implemented into the ABP also by other groups studying the impact of the gene deletion on steroid profile analysis …”

“…Due to its critical role, the addition of the athletes' UGT2B17 genotype has been suggested to be implemented into the ABP also by other groups studying the impact of the gene deletion on steroid profile analysis. [76] Alternative to the monovariate adaptive model currently employed in the ABP, Alladio et al investigated potential advantages of multivariate statistical approaches, utilizing the same urinary steroids commonly monitored in routine doping controls. [77] In a proof-of-concept study using principal component analysis (PCA) and Hotelling T [2] test, the principle applicability of the strategy was successfully demonstrated.…”