Impact of the UGT2B17 polymorphism on the steroid profile. Results of a crossover clinical trial in athletes submitted to testosterone administration

Impact of the UGT2B17 polymorphism on the steroid profile. Results of a crossover clinical trial in athletes submitted to testosterone administration / Pilar Martín-Escudero, Jesús A. Muñoz-Guerra, Soledad Vargas García-Tenorio, Ester Serrano Garde, Ana B. Soldevilla-Navarro, Mercedes Galindo-Canales, Nayade Prado, Manuel E. Fuentes-Ferrer, Cristina Fernández-Pérez. - (Steroids 141 (2019) January; p. 104-113)

  • PMID: 30503386
  • DOI: 10.1016/j.steroids.2018.11.009


Abstract

This article studies the genetic influence of polymorphism of the UGT2B17 gen on the urinary steroid profile and its implications for the anti-doping field. The study presents the results of a triple-blind randomized placebo-controlled crossover trial with healthy athletes submitted to a single dose of 250 mg of testosterone cypionate. Forty urine samples were collected from each participant. Mass spectrometry-based techniques commonly used in Anti-Doping laboratories, were employed to measure the urinary concentration and the Δδ13C values of a selection of target compounds for testosterone (T) administration together with LH. Twelve volunteers were included in the study; the polymorphism was evenly distributed among them. After T administration, the most meaningful change affected the Testosterone/Epitestosterone ratio (T/E) and the urinary concentration of LH. In relation with T/E, the wild type homozygous (ins/ins) group there was a mean relative increase of 30 (CI 95%: 25.2 to 36.7); in the heterozygous mutant (del/ins) group it was 19.8 (CI 95%:15.9 to 24.7); and in the homozygous mutant (del/del) group it was 19.7 (CI 95% 14.9 to 26.2). In the case of LH, it́s observed how LH values decrease significantly after the administration of Testex homogeneously among the three groups. The main outcome was related to the (del/del) group (homozygous mutant), where due to the depressed basal level of the steroid profile, if the longitudinal steroid profile of the athlete was not available, the analysis by GC/MS would not produce an "atypical" result according to the WADA TD2016EAAS despite the T administration. However, the genotyping of the UGT2B17 polymorphism, the follow up of LH and the use of GC-C-IRMS makes it possible to identify most of these samples as Adverse.

Original document

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Science
Study
Date
29 November 2018
People
Fernández-Pérez, Cristina
Fuentes-Ferrer, Manuel E.
Galindo-Canales, Mercedes
García-Tenorio, Soledad Vargas
Garde, Ester Serrano
Martín-Escudero, Pilar
Muñoz-Guerra, Jesús A.
Prado, Mayade
Soldevilla-Navarro, Ana B.
Country
Spain
Language
English
Other organisations
Agencia Española de Protección de la Salud en el Deporte (AEPSAD) - Spanish Agency for the Protection of Health in Sport
Hospital Clínico San Carlos
Universidad Complutense de Madrid - Complutense University of Madrid
Laboratories
Madrid, Spain: Madrid Anti-Doping Laboratory Agencia Española de Protección de la Salud en el Deporte
Analytical aspects
Mass spectrometry analysis
Testing method development
Doping classes
S1. Anabolic Agents
Substances
Luteinizing hormone (LH)
T/E ratio (testosterone / epitestosterone)
Testosterone
Document category
Scientific article
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Date generated
31 March 2021
Date of last modification
15 April 2021
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