title: UDP-glucuronosyltransferase 2B17 genotyping in Japanese athletes and evaluation of the current sports drug testing for detecting testosterone misuse.
abstract: Ethnicity has been found to influence urinary testosterone glucuronide to epitestosterone glucuronide (T/E) ratios among athletes. Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) is the most active enzyme in testosterone glucuronidation. UGT2B17 polymorphism analysis is rarely performed in Japanese athletes, and the influence of testosterone administration on steroid profiles and carbon isotope ratios, according to gene polymorphisms, in Asians remains unknown. The prevalence of UGT2B17 genotypes and urinary androgenic steroid profiles, classified according to UGT2B17 genotypes, was investigated in Japanese athletes (255 male and 256 female). Testosterone enanthate (100 mg) was administered intramuscularly to Japanese female volunteers (del/del: n = 6, del/ins: n = 3, ins/ins: n = 1). The distribution rates of the UGT2B17 del/del genotype in Japanese male and female athletes were 74.5% and 60.2%, respectively. The ins/ins genotype was detected in only three male (1.2%) and seven female (2.7%) athletes. The prevalence of the UGT2B17 deletion genotype was extremely high in Japanese athletes. The T/E ratio in the del/del group was significantly lower than that in the other groups. After testosterone was administered to female volunteers, the T/E ratios for the del/del individuals failed to reach the positivity criterion of 4. By contrast, in all of the del/del subjects, the gas chromatography/combustion/isotope ratio mass spectrometry (GC-C-IRMS) analysis successfully fulfilled the positivity criterion. The overall result has demonstrated the limited effectiveness of population-based T/E ratios in screening tests for testosterone use. Subject-based steroid profiling with UGT2B17 genotyping will be an effective strategy for detecting testosterone misuse.
authors.affiliation: Anti-Doping Laboratory, Mitsubishi Chemical Medience Corporation, 3-30-1 Shimura, Itabashi-ku, Tokyo, 174-8555, Japan. okano.masato@mk.medience.co.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Okano
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ueda
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nishitani
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kano
authors.forename: Ayako
authors.initials: A
authors.lastname: Ikekita
authors.forename: Shinji
authors.initials: S
authors.lastname: Kageyama
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D056352:Athletes; D004845:Epitestosterone / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D017353:Gene Deletion; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D015813:Substance Abuse Detection / Q000379:methods*; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000652:urine*; D055815:Young Adult
chemical_list: D015778:Minor Histocompatibility Antigens; C015529:testosterone glucuronate; D013739:Testosterone; D004845:Epitestosterone; C004648:testosterone enanthate; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human