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.

中文翻译：

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标准化的睾丸激素葡萄糖醛酸作为7-18岁儿童中高度可变的UGT2B17的潜在尿液生物标志物。

UDP-葡萄糖醛酸糖基转移酶2B17（UGT2B17）是高度可变的雄激素代谢和药物代谢酶。UGT2B17表现出独特的个体发育特征，其特征是从青春期前到成年期肝蛋白表达急剧增加。年龄，性别，拷贝数变异（CNV）和单核苷酸多态性仅能解释蛋白质表达变异性的26％，突显了需要一种表型生物标记物来预测UGT2B17底物葡萄糖苷酸化的个体变异性。在这里，我们提出将睾丸激素葡糖醛酸（TG）通过雄甾酮葡萄糖醛酸（TG / AG）标准化作为尿UGT2B17生物标志物，并检查尿TG / AG与年龄，性别和CNV之间的关联。我们对63名7-18岁的儿科受试者进行了12种雄激素结合物的靶向代谢组学与液相色谱串联质谱分析，并在3年​​内进行了7次随访。与UGT2B17蛋白表达的发展轨迹相一致，尿TG / AG与年龄，性别和CNV显着相关。总之，TG / AG显示出有望作为尿液UGT2B17表型生物标志物。