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    UDP-glucuronosyltransferase 2B17 (UGT2B17) is a highly variable androgen-metabolizing and drug-metabolizing enzyme. UGT2B17 exhibits a unique ontogeny profile characterized by a dramatic increase in hepatic protein expression from prepubertal 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 interindividual 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 among urinary TG/AG and age, sex, and CNV. We performed targeted metabolomics of 12 androgen conjugates with liquid-chromatography tandem mass spectrometry in 63 pediatric subjects ages 7-18 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. © 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.

    Citation

    Haeyoung Zhang, Abdul Basit, Chris Wolford, Kuan-Fu Chen, Andrea Gaedigk, Yvonne S Lin, J Steven Leeder, Bhagwat Prasad. Normalized Testosterone Glucuronide as a Potential Urinary Biomarker for Highly Variable UGT2B17 in Children 7-18 Years. Clinical pharmacology and therapeutics. 2020 May;107(5):1149-1158

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    PMID: 31900930

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