title: Doping test results dependent on genotype of uridine diphospho-glucuronosyl transferase 2B17, the major enzyme for testosterone glucuronidation.
abstract: BACKGROUND
  Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. The large variation in testosterone glucuronide (TG) excretion and its strong association with a deletion polymorphism in the uridine diphospho-glucuronosyl transferase (UGT) 2B17 gene challenge the accuracy of the T/E ratio test.
  
  
  OBJECTIVE
  Our objective was to investigate whether genotype-based cutoff values will improve the sensitivity and specificity of the test.
  
  
  METHODS
  This was an open three-armed comparative study.
  
  
  METHODS
  A total of 55 healthy male volunteers with either two, one, or no allele [insertion/insertion, insertion/deletion, or deletion/deletion (del/del)] of the UGT2B17 gene was included in the study.
  
  
  METHODS
  A single im dose of 500 mg testosterone enanthate was administered.
  
  
  METHODS
  Urinary excretion of TG after dose and the T/E ratio during 15 d were calculated.
  
  
  RESULTS
  The degree and rate of increase in the TG excretion rate were highly dependent on the UGT2B17 genotype with a 20-fold higher average maximum increase in the insertion/insertion group compared with the del/del group. Of the del/del subjects, 40% never reached the T/E ratio of 4.0 on any of the 15 d after the dose. When differentiated cutoff levels for the del/del (1.0) and the other genotypes (6.0) were applied, the sensitivity increased substantially for the del/del group, and false positives in the other genotypes were eliminated.
  
  
  CONCLUSIONS
  Consideration of the genetic variation in disposition of androgens will improve the sensitivity and specificity of the testosterone doping test. This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society.
authors.affiliation: Clinical Pharmacology C1:68, Karolinska University Hospital, Huddinge, Stockholm, Sweden. jenny.schulze@ki.se
authors.forename: Jenny Jakobsson
authors.initials: JJ
authors.lastname: Schulze
authors.forename: Jonas
authors.initials: J
authors.lastname: Lundmark
authors.forename: Mats
authors.initials: M
authors.lastname: Garle
authors.forename: Ilona
authors.initials: I
authors.lastname: Skilving
authors.forename: Lena
authors.initials: L
authors.lastname: Ekström
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
mesh_terms: D000293:Adolescent; D000328:Adult; D004300:Doping in Sports; D004845:Epitestosterone / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D018628:Gene Dosage; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D012680:Sensitivity and Specificity; D019966:Substance-Related Disorders / Q000175:diagnosis*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine
chemical_list: D015778:Minor Histocompatibility Antigens; C015529:testosterone glucuronate; D013739:Testosterone; D004845:Epitestosterone; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human