Human Hepatic UGT2B15 Developmental Expression

Human hepatic UGT2B15 developmental expression changes may alter the metabolism of important drugs and toxicants such as bisphenol A (BPA). Previously, UGT2B15 ontogeny knowledge consisted of transcript data, a dubious surrogate for protein expression. Herein, UGT2B15 protein content was determined in human hepatic microsomes (n = 236, 8 weeks gestation to 18 years). The impact of a common, functional single nucleotide polymorphism (g.253G>T), present in UGT2B15*2 and *5 alleles, was also tested. UGT2B15 expression began during late fetal life, at about 18% of mature values (medians = 48, 267 pmoles/mg of microsomal protein, respectively; p < 0.001). UGT2B15 neonatal (n = 39) and late fetal (≥28 weeks, n = 10) content was similar, but lower than that of infants between 3 and 15 weeks age (n = 46; medians = 38, 48, 404 pmoles/mg microsomal protein, respectively; p < 0.001). Values for the latter group were higher compared with the remaining age group (15 weeks to 18 years; n = 82, p < 0.001). UGT2B15 expression varied 31-fold across the entire sample, and within groups, ranged from 4- to 27-fold. Among postnatal samples, age group, the presence of g.253T and male gender were each significantly associated with greater UGT2B15 expression (p < 0.001, <0.01, and <0.05, respectively; stepwise linear regression). In summary, hepatic UGT2B15 protein onset begins in late gestation; however, the greatest rate of change occurs during the first few weeks after birth. We speculate that the fetus and neonate may have lower clearance of some UGT2B15 substrates, such as BPA, compared with older individuals.