Normalized Testosterone Glucuronide as a Potential Urinary Biomarker for Highly Variable UGT2B17 in Children 7-18 Years

• Published in: Clinical pharmacology and therapeutics Vol. 107; no. 5; p. 1149
• Main Authors: Zhang, Haeyoung, Basit, Abdul, Wolford, Chris, Chen, Kuan-Fu, Gaedigk, Andrea, Lin, Yvonne S, Leeder, J Steven, Prasad, Bhagwat
• Format: Journal Article
• Language: English
• Published: United States 01.05.2020
• Subjects: Adolescent; Age Factors; Biomarkers - urine; Child; DNA Copy Number Variations; Female; Glucuronosyltransferase - genetics; Humans; Liver - metabolism; Male; Metabolomics; Minor Histocompatibility Antigens - genetics; Polymorphism, Single Nucleotide; Sex Factors; Testosterone - analogs & derivatives; Testosterone - urine
• ISSN: 1532-6535
• DOI: 10.1002/cpt.1764

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.