title: Substantial advantage of a combined Bayesian and genotyping approach in testosterone doping tests.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet at Division of Clinical Pharmacology, Karolinska University Hospital, SE-141 86 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: Lena
authors.initials: L
authors.lastname: Ekström
authors.forename: Pierre-Edouard
authors.initials: PE
authors.lastname: Sottas
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
mesh_terms: 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
chemical_list: D015778:Minor Histocompatibility Antigens; D013739:Testosterone; D004845:Epitestosterone; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human