Doping test results dependent on genotype of uridine diphospho-glucuronosyl transferase 2B17, the major enzyme for testosterone glucuronidation.
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.
Schulze
Jenny Jakobsson
JJ
Clinical Pharmacology C1:68, Karolinska University Hospital, Huddinge, Stockholm, Sweden. jenny.schulze@ki.se
Lundmark
Jonas
J
Garle
Mats
M
Skilving
Ilona
I
Ekström
Lena
L
Rane
Anders
A
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
D015778:Minor Histocompatibility Antigens; C015529:testosterone glucuronate; D013739:Testosterone; D004845:Epitestosterone; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human