Genetic aspects of epitestosterone formation and androgen disposition: influence of polymorphisms in CYP17 and UGT2B enzymes

Schulze, Jenny J.; Lorentzon, Mattias; Ohlsson, Claes; Lundmark, Jonas; Roh, Hyung‐Keun; Rane, Anders; Ekström, Lena

doi:10.1097/fpc.0b013e3282fad38a

Cited by 49 publications

(54 citation statements)

References 39 publications

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“…We have demonstrated that a common deletion polymorphism in the gene coding for uridine diphosphate-glucuronosyltranferase (UGT) 2B17 (11) is strongly associated with testosterone glucuronide levels in urine (4) and that 40% of the individuals lacking the UGT2B17 gene would never reach the cutoff ratio of 4.0 used today after a single dose of 360 mg testosterone (6). We have also shown that a thymine greater than a thymine/cytosine (A1/A2) promoter polymorphism in the CYP17 gene is associated with lower urinary epitestosterone excretion resulting in 64% higher T/E ratios in homozygotes, increasing the risk of false-positive doping test results (12). Sottas et al (reviewed in Ref.…”

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confidence: 87%

Androgen Sulfation in Healthy UDP-Glucuronosyl Transferase 2B17 Enzyme-Deficient Men

Schulze

Thörngren

Garle

et al. 2011

The Journal of Clinical Endocrinology & Metabolism

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confidence: 87%

Androgen Sulfation in Healthy UDP-Glucuronosyl Transferase 2B17 Enzyme-Deficient Men

Schulze

Thörngren

Garle

et al. 2011

The Journal of Clinical Endocrinology & Metabolism

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“…There are also individuals that have naturally high T/E ratios due to decreased excretion of epitestosterone. In males, part of this low epitestosterone excretion can be explained by a promoter polymorphism in the CYP17 gene (13), resulting in 64% higher T/E ratios in men homozygous for the T allele (14). However, this polymorphism in relation to epitestosterone excretion has not been studied in women.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Genetics and Hormonal Contraceptives on the Steroid Profile in Female Athletes

et al. 2014

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The steroid module of the Athlete Biological Passport, the newest innovation in doping testing, is currently being finalized for implementation. Several factors, other than doping, can affect the longitudinal steroid profile. In this study, we investigated the effect of hormonal contraceptives (HC) as well as the effect of three polymorphisms on female steroid profiles in relation to doping controls. The study population consisted of 79 female elite athletes between the ages of 18 and 45. HC were used by 32% of the subjects. A full urinary steroid profile was obtained using World Anti-Doping Agency accredited methods. In addition all subjects were genotyped for copy number variation of UGT2B17 and SNPs in UGT2B7 and CYP17. Subjects using HC excreted 40% less epitestosterone as compared to non-users (p = 0.005) but showed no difference in testosterone excretion. When removing individuals homozygous for the deletion in UGT2B17, the testosterone to epitestosterone (T/E) ratio was 29% higher in the HC group (p = 0.016). In agreement with previous findings in men, copy number variation of UGT2B17 had significant effect on female urinary testosterone excretion and therefore also the T/E ratio. Subjects homozygous for the T allele of CYP17 showed a lower urinary epitestosterone concentration than the other CYP17 genotypes. It is of great importance that the athlete’s steroidal passport can compensate for all possible normal variability in steroid profiles from women. Therefore, considering the large impact of HC on female steroid profiles, we suggest that the use of HC should be a mandatory question on the doping control form.

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“…Genotyping of UGT2B17 deletion polymorphism was performed using real-time PCR as described previously (Schulze et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

Tissue Distribution and Relative Gene Expression of UDP-Glucuronosyltransferases (2B7, 2B15, 2B17) in the Human Fetus

2012

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UDP-glucuronosyltransferases (UGTs) catalyze phase II conjugation reactions and play an important role in the inactivation and elimination of several drugs. It is well known that the UGT activity in fetal livers is low compared with the UGT activity in adult livers. In this study the mRNA expression levels of the three human subfamilies, 2B7, 2B15, and 2B17, were determined in 20 adult and 60 fetal liver tissue specimens. The expression profile in fetal kidneys (N = 43), adrenals (N = 46), and lungs (N = 37) was also determined. All fetal and adult samples were genotyped for the UGT2B17 deletion polymorphism. Adult liver contained 13-36 times higher levels of UGT2B mRNAs as compared with fetal livers. UGT2B7 was most abundant in fetal lungs and kidneys, whereas UGT2B15 and UGT2B17 were predominant in the liver. There was a significant correlation between UGT2B7 expression levels in lungs and kidneys, whereas for the other UGT2Bs no correlation between the different tissues was observed. Fetuses expressing two UGT2B17 alleles (ins/ins) displayed significantly higher levels of UGT2B17 mRNA compared to ins/del fetuses in lungs, whereas in the other tissues no gene dose-effect was observed.

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Genetic aspects of epitestosterone formation and androgen disposition: influence of polymorphisms in CYP17 and UGT2B enzymes

Cited by 49 publications

References 39 publications

Androgen Sulfation in Healthy UDP-Glucuronosyl Transferase 2B17 Enzyme-Deficient Men

Androgen Sulfation in Healthy UDP-Glucuronosyl Transferase 2B17 Enzyme-Deficient Men

The Impact of Genetics and Hormonal Contraceptives on the Steroid Profile in Female Athletes

Tissue Distribution and Relative Gene Expression of UDP-Glucuronosyltransferases (2B7, 2B15, 2B17) in the Human Fetus

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