Normalized testosterone glucuronide (TG/AG) as a potential urinary biomarker for highly variable UGT2B17 in children 7 to 18 years.Clin Pharmacol Ther 2020CP
UDP-glucuronosyltransferase 2B17 (UGT2B17) is a highly variable androgen- and drug-metabolizing enzyme. UGT2B17 exhibits a unique ontogeny profile characterized by a dramatic increase in hepatic protein expression from pre-pubertal age to adulthood. Age, sex, copy number variation (CNV), and single nucleotide polymorphisms only explain 26% of variability in protein expression, highlighting the need for a phenotypic biomarker for predicting inter-individual variability in glucuronidation of UGT2B17 substrates. Here we propose testosterone glucuronide (TG) normalized by androsterone glucuronide (TG/AG) as a urinary UGT2B17 biomarker, and examine the associations between urinary TG/AG and age, sex, and CNV. We performed targeted metabolomics of 12 androgen conjugates with LC-MS/MS in 63 pediatric subjects ages 7 to 18 years followed over 7 visits in 3 years. Consistent with the reported developmental trajectory of UGT2B17 protein expression, urinary TG/AG is significantly associated with age, sex, and CNV. In conclusion, TG/AG shows promise as a phenotypic urinary UGT2B17 biomarker.