Sex steroid levels and cortical bone size in young men are associated with a uridine diphosphate glucuronosyltransferase 2B7 Polymorphism (H268Y)

Context: Sex steroids are involved in the regulation of pubertal cortical bone expansion in males. In vitro studies have indicated that the enzyme uridine diphosphate glucuronosyltransferase (UGT) 2B7 has the capacity to glucuronidate sex steroids and their metabolites. Objective: Our objective was to determine the impact of the (HY)-Y-268 polymorphism in the UGT2B7 gene on interindividual variation of serum levels of sex steroids and cortical bone dimensions. Participants: The population-based cohort Gothenburg Osteoporosis and Obesity Determinants study consists of 1068 young adult Swedish men ( age 18.9 yr). Main Outcome Measures: Serum levels of sex steroids and the three major glucuronidated androgen metabolites, androstane-3 alpha, 17 beta-diol- 17glucuronide, androstane- 3 alpha, 17 beta- diol-3glucuronide, and androsterone-glucuronide, were analyzed. Cortical and trabecular volumetric bone mineral density and cortical bone size were measured by peripheral quantitative computer tomography. Results: Serum levels of testosterone (YY 9% over HH; P < 0.01), dihydrotestosterone (YY 10% over HH; P < 0.01), and estradiol ( YY 8% over HH; P < 0.01) were associated with the UGT2B7 H268Y polymorphism. The polymorphism was associated with androstane3 alpha, 17 beta- diol-17glucuronide and androstane- 3 alpha, 17 beta- diol-3glucuronide ( P < 0.01), but not with androsterone-glucuronide serum levels. In addition, the UGT2B7 H268Y polymorphism was an independent predictor of cortical bone size, reflected by periosteal circumference and cortical moment of inertia ( P < 0.01), in both the weight-bearing tibia and nonweight-bearing radius. Conclusions: The UGT2B7 H268Y polymorphism is independently associated with cortical bone size and serum sex steroid levels in young adult men. Subjects homozygous for the Y allele had higher serum testosterone and larger cortical bone size than subjects homozygous for the H allele. However, the underlying mechanism behind these associations is unknown and has to be studied further.