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Premature pubarche (PP) appears to be a risk factor for the subsequent development of polycystic ovary syndrome (PCOS) during or after puberty. The clinical manifestations due to hyperandrogenism are influenced by androgen production, androgen metabolism, and androgen receptor activity. Glucuronidation by the UDP-glucuronyltransferase 2B (UGT2B) family of enzymes is one mechanism through which androgens are inactivated. Two variants differing by the amino acid at codon 85 have been described for UGT2B15, a member of this family. Both variants show similar substrate specificities. However, for the substrates alpha-androstanediol (alpha-diol) and dihydrotestosterone (DHT), the D85 variant has a lower Vmax than the Y85 variant. We compared the frequencies of these variants in 69 patients with PP, 46 adolescent girls with hyperandrogenism (HA), and 88 healthy controls to determine whether the frequency of the D85 variant was increased among patients with hyperandrogenism. Allele frequencies were comparable in children with PP, adolescent girls with HA, and healthy control subjects. Although D85 and Y85 appear to be common variants, we cannot exclude the possibility that the UGT2B15 gene represents a minor modifying locus.

Frequencies of the D85 and Y85 Variants of UGT2B1S in Children and Adolescent Girls with Hyperandrogenism