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Sex Steroid Levels and Cortical Bone Size in Young Men Are Associated with a Uridine Diphosphate Glucuronosyltransferase 2B7 Polymorphism (H²⁶⁸Y)

Center for Bone Research at the Sahlgrenska Academy (C.S., M.L., L.V., C.O.), Department of Internal Medicine, Gothenburg University, SE-41345 Gothenburg, Sweden; Laboratory of Molecular Endocrinology and Oncology (F.L., S.C., A.B.), Laval University Hospital Research Center and Laval University, Québec, Canada, G1V 4G2; and Department of Laboratory Medicine (A.R., J.J.), Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, SE-141 86 Stockholm, Sweden

Address all correspondence and requests for reprints to: Claes Ohlsson, M.D., Ph.D., Professor, Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden. E-mail: Claes.Ohlsson{at}medic.gu.se.

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 H²⁶⁸Y 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-3,17ß-diol-17glucuronide, androstane-3,17ß-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 androstane-3,17ß-diol-17glucuronide and androstane-3,17ß-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.

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