Substantial advantage of a combined Bayesian and genotyping approach in testosterone doping tests.
Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. A deletion polymorphism in the gene coding for UGT2B17 is strongly associated with reduced testosterone glucuronide (TG) levels in urine. Many of the individuals devoid of the gene would not reach a T/E ratio of 4.0 after testosterone intake. Future test programs will most likely shift from population based- to individual-based T/E cut-off ratios using Bayesian inference. A longitudinal analysis is dependent on an individual's true negative baseline T/E ratio. The aim was to investigate whether it is possible to increase the sensitivity and specificity of the T/E test by addition of UGT2B17 genotype information in a Bayesian framework. A single intramuscular dose of 500mg testosterone enanthate was given to 55 healthy male volunteers with either two, one or no allele (ins/ins, ins/del or del/del) of the UGT2B17 gene. Urinary excretion of TG and the T/E ratio was measured during 15 days. The Bayesian analysis was conducted to calculate the individual T/E cut-off ratio. When adding the genotype information, the program returned lower individual cut-off ratios in all del/del subjects increasing the sensitivity of the test considerably. It will be difficult, if not impossible, to discriminate between a true negative baseline T/E value and a false negative one without knowledge of the UGT2B17 genotype. UGT2B17 genotype information is crucial, both to decide which initial cut-off ratio to use for an individual, and for increasing the sensitivity of the Bayesian analysis.
Schulze
Jenny Jakobsson
JJ
Department of Laboratory Medicine, Karolinska Institutet at Division of Clinical Pharmacology, Karolinska University Hospital, SE-141 86 Stockholm, Sweden. jenny.schulze@ki.se
Lundmark
Jonas
J
Garle
Mats
M
Ekström
Lena
L
Sottas
Pierre-Edouard
PE
Rane
Anders
A
D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D004300:Doping in Sports; D004845:Epitestosterone / Q000652:urine; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic / Q000235:genetics*; D015813:Substance Abuse Detection / Q000379:methods*; D013739:Testosterone / Q000652:urine*; D055815:Young Adult
D015778:Minor Histocompatibility Antigens; D013739:Testosterone; D004845:Epitestosterone; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human