Deletion in the uridine diphosphate glucuronyltransferase 2B17 gene is associated with delayed pubarche in healthy boys

OBJECTIVE: Only a few genetic loci are known to be associated with male pubertal events. The ability of excreting testosterone (T) and other steroids in the urine depends on sulfation and glucuronidation. One of several essential glucuronidases is encoded by the UGT2B17 gene. In a preliminary report, we found that homozygous deletion of UGT2B17 in boys was associated with lower urinary excretion of T. We hypothesized that boys with a lower glucuronidation capacity may have altered androgen action and excretion affecting pubarche, as this represents a T-dependent event. DESIGN, PARTICIPANTS AND MEASURES: 668 healthy boys (cross-sectional) aged 6.1–21.9 years (COPENHAGEN puberty study conducted from 2005 to 2006) were included. 65 of the boys where followed longitudinally every 6 months. Participants were genotyped for UGT2B17 copy number variation (CNV). Clinical pubertal staging including orchidometry, anthropometry and serum reproductive hormone levels. RESULTS: 59 of the 668 boys (8.8%) presented with a homozygous deletion of UGT2B17 (del/del). These boys experienced pubarche at a mean age of 12.73 years (12.00–13.46) vs 12.40 years (12.11–12.68) in boys heterozygous for deletion of UGT2B17 (del/ins) vs 12.06 years (11.79–12.33) in boys with the wild-type genotype (ins/ins) (P = 0.029, corrected for BMI z-score). The effect accounted for 0.34 years delay per allele (95% CI: 0.03–0.64). A comparable trend was observed for onset of testicular enlargement >3 mL but did not reach significance. CONCLUSION: CNV of UGT2B17 is a factor contributing to the timing of male pubarche.