Substantial advantage of a combined Bayesian and genotyping approach in testosterone doping tests |
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Authors: | Jenny Jakobsson Schulze Jonas Lundmark Lena Ekström Anders Rane |
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Institution: | a Department of Laboratory Medicine, Karolinska Institutet at Division of Clinical Pharmacology, Karolinska University Hospital, SE-141 86 Stockholm, Sweden b Swiss Laboratory for Doping Analyses, University of Lausanne, Chemin des Croisetes 22, 1066 Epalinges, Switzerland |
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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 500 mg 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. |
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Keywords: | UGT2B17 deletion polymorphism Bayesian statistics T/E ratio Testosterone doping Longitudinal analysis |
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